HLA-DP: A Class II Restriction Molecule Involved in Epitope Spreading During the Development of Multiple Sclerosis
Identifieur interne : 001E46 ( Istex/Corpus ); précédent : 001E45; suivant : 001E47HLA-DP: A Class II Restriction Molecule Involved in Epitope Spreading During the Development of Multiple Sclerosis
Auteurs : Min Yu ; R. Philip Kinkel ; Bianca Weinstock-Guttman ; Daniel J. Cook ; Vincent K. TuohySource :
- Human Immunology [ 0198-8859 ] ; 1998.
English descriptors
- KwdEn :
- Teeft :
- Allele, American society, Amino acid, Animal cell cultures, Autologous serum, Autoreactivity, Becton dickinson, Cell epitope, Cell lines, Cell recognition, Cell response, Cell responses, Cerebrospinal fluid, Cervical myelitis, Cleveland clinic foundation, Clinical course, Clinical progression, Complete disparity, Control peptide, Control subjects, Control wells, Determinant, Disease outcome, Disease risk, Dual restriction, Early development, Early stages, Elsevier science, Encephalitogenic determinant, Epitope, European collection, Extensive plasticity, Falcon plates, Fine specificity, Glass fiber filters, Haplotype, Hepes buffer, Homozygous typing, Human immunol, Human immunology, Imds, Imds patients, Imds subjects, Immunodominant myelin, Immunol, Important role, Initial onset, Linkage disequilibrium, Lysis, Microtiter falcon plates, Molecular analysis, Monosymptomatic demyelination syndromes, Month period, Multiple sclerosis, Multiple sclerosis patients, Mycobacteria tuberculosis, Myelin, Myelin oligodendrocyte glycoprotein, Myelin proteins, Myelin proteolipid protein, Neuroimmunol, Neurologic, Neurologic symptoms, Pbmc, Peptide, Peptide series, Permissive alleles, Present study, Proc natl acad, Proliferative, Proliferative responses, Protein peptide, Proteolipid, Proteolipid protein, Restriction element, Restriction molecule, Risk factor, Scintillation spectrometry, Sclerosis, Several reports, Specific lysis, Spontaneous release, Stimulation index, Study protocol, Study subjects, Susceptibility, Systemic sclerosis, Target cell lysis, Target cells, Tetanus toxoid, Tissue antigens, Total incorporation, Total volume, Tuohy, Variable rates.
Abstract
Abstract: ABSTRACT: Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system. It is widely believed that complex polygenic inheritance patterns involving HLA-DR and -DQ class II genes contribute to MS susceptibility, and current evidence indicates that disease risk vs disease outcome may be associated with distinctly different HLA class II alleles. We have recently shown that the early development of MS is accompanied by an extensive plasticity of myelin self-recognition with the acquisition of neo-autoreactivity, or epitope spreading, as a prominent feature. Although we did not observe a common determinant recognized by patients sharing identical HLA-DR or -DQ class II alleles, we did observe epitope spreading to the p50–63 determinant of myelin proteolipid protein (PLP) in two study subjects showing complete disparity at HLA-DR and -DQ but identity at the HLA-DP allele DPB1∗0301. In the present study we show that self-recognition during the early stages in the development of MS involves HLA-DP class II restricted responses to the PLP 50–63 spreading determinant. Our results suggest that self-presentation by HLA-DP may play an important role in epitope spreading and in the propagation of self-recognition during the clinical progression of MS.
Url:
DOI: 10.1016/S0198-8859(97)00252-8
Links to Exploration step
ISTEX:9D16647DA0308237F9397AE0BC33DB40122A26FELe document en format XML
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Philip Kinkel</name><affiliation><mods:affiliation>Mellen Center for Multiple Sclerosis Research and Treatment (R.P.K., B.W.G., V.K.T.), The Cleveland Clinic Foundation, Cleveland, OH, 44195, USA,</mods:affiliation></affiliation></author><author><name sortKey="Weinstock Guttman, Bianca" sort="Weinstock Guttman, Bianca" uniqKey="Weinstock Guttman B" first="Bianca" last="Weinstock-Guttman">Bianca Weinstock-Guttman</name><affiliation><mods:affiliation>Mellen Center for Multiple Sclerosis Research and Treatment (R.P.K., B.W.G., V.K.T.), The Cleveland Clinic Foundation, Cleveland, OH, 44195, USA,</mods:affiliation></affiliation></author><author><name sortKey="Cook, Daniel J" sort="Cook, Daniel J" uniqKey="Cook D" first="Daniel J." last="Cook">Daniel J. 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Philip" last="Kinkel">R. Philip Kinkel</name><affiliation><mods:affiliation>Mellen Center for Multiple Sclerosis Research and Treatment (R.P.K., B.W.G., V.K.T.), The Cleveland Clinic Foundation, Cleveland, OH, 44195, USA,</mods:affiliation></affiliation></author><author><name sortKey="Weinstock Guttman, Bianca" sort="Weinstock Guttman, Bianca" uniqKey="Weinstock Guttman B" first="Bianca" last="Weinstock-Guttman">Bianca Weinstock-Guttman</name><affiliation><mods:affiliation>Mellen Center for Multiple Sclerosis Research and Treatment (R.P.K., B.W.G., V.K.T.), The Cleveland Clinic Foundation, Cleveland, OH, 44195, USA,</mods:affiliation></affiliation></author><author><name sortKey="Cook, Daniel J" sort="Cook, Daniel J" uniqKey="Cook D" first="Daniel J." last="Cook">Daniel J. Cook</name><affiliation><mods:affiliation>Histocompatibility Laboratory (D.J.C.), The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.</mods:affiliation></affiliation></author><author><name sortKey="Tuohy, Vincent K" sort="Tuohy, Vincent K" uniqKey="Tuohy V" first="Vincent K." last="Tuohy">Vincent K. Tuohy</name><affiliation><mods:affiliation>Department of Immunology, The Cleveland Clinic Foundation, Cleveland, OH, 44195, USA (M.Y., V.K.T.),</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Human Immunology</title><title level="j" type="abbrev">HIM</title><idno type="ISSN">0198-8859</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1998">1998</date><biblScope unit="volume">59</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="15">15</biblScope><biblScope unit="page" to="24">24</biblScope></imprint><idno type="ISSN">0198-8859</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0198-8859</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>CNS</term><term>EAE</term><term>FMOC</term><term>HPLC</term><term>HTC</term><term>IMDS</term><term>MAG</term><term>MBP</term><term>MOG</term><term>MRI</term><term>MS</term><term>OND</term><term>PBMC</term><term>PCR-SSOP</term><term>PLP</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Allele</term><term>American society</term><term>Amino acid</term><term>Animal cell cultures</term><term>Autologous serum</term><term>Autoreactivity</term><term>Becton dickinson</term><term>Cell epitope</term><term>Cell lines</term><term>Cell recognition</term><term>Cell response</term><term>Cell responses</term><term>Cerebrospinal fluid</term><term>Cervical myelitis</term><term>Cleveland clinic foundation</term><term>Clinical course</term><term>Clinical progression</term><term>Complete disparity</term><term>Control peptide</term><term>Control subjects</term><term>Control wells</term><term>Determinant</term><term>Disease outcome</term><term>Disease risk</term><term>Dual restriction</term><term>Early development</term><term>Early stages</term><term>Elsevier science</term><term>Encephalitogenic determinant</term><term>Epitope</term><term>European collection</term><term>Extensive plasticity</term><term>Falcon plates</term><term>Fine specificity</term><term>Glass fiber filters</term><term>Haplotype</term><term>Hepes buffer</term><term>Homozygous typing</term><term>Human immunol</term><term>Human immunology</term><term>Imds</term><term>Imds patients</term><term>Imds subjects</term><term>Immunodominant myelin</term><term>Immunol</term><term>Important role</term><term>Initial onset</term><term>Linkage disequilibrium</term><term>Lysis</term><term>Microtiter falcon plates</term><term>Molecular analysis</term><term>Monosymptomatic demyelination syndromes</term><term>Month period</term><term>Multiple sclerosis</term><term>Multiple sclerosis patients</term><term>Mycobacteria tuberculosis</term><term>Myelin</term><term>Myelin oligodendrocyte glycoprotein</term><term>Myelin proteins</term><term>Myelin proteolipid protein</term><term>Neuroimmunol</term><term>Neurologic</term><term>Neurologic symptoms</term><term>Pbmc</term><term>Peptide</term><term>Peptide series</term><term>Permissive alleles</term><term>Present study</term><term>Proc natl acad</term><term>Proliferative</term><term>Proliferative responses</term><term>Protein peptide</term><term>Proteolipid</term><term>Proteolipid protein</term><term>Restriction element</term><term>Restriction molecule</term><term>Risk factor</term><term>Scintillation spectrometry</term><term>Sclerosis</term><term>Several reports</term><term>Specific lysis</term><term>Spontaneous release</term><term>Stimulation index</term><term>Study protocol</term><term>Study subjects</term><term>Susceptibility</term><term>Systemic sclerosis</term><term>Target cell lysis</term><term>Target cells</term><term>Tetanus toxoid</term><term>Tissue antigens</term><term>Total incorporation</term><term>Total volume</term><term>Tuohy</term><term>Variable rates</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: ABSTRACT: Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system. It is widely believed that complex polygenic inheritance patterns involving HLA-DR and -DQ class II genes contribute to MS susceptibility, and current evidence indicates that disease risk vs disease outcome may be associated with distinctly different HLA class II alleles. We have recently shown that the early development of MS is accompanied by an extensive plasticity of myelin self-recognition with the acquisition of neo-autoreactivity, or epitope spreading, as a prominent feature. Although we did not observe a common determinant recognized by patients sharing identical HLA-DR or -DQ class II alleles, we did observe epitope spreading to the p50–63 determinant of myelin proteolipid protein (PLP) in two study subjects showing complete disparity at HLA-DR and -DQ but identity at the HLA-DP allele DPB1∗0301. In the present study we show that self-recognition during the early stages in the development of MS involves HLA-DP class II restricted responses to the PLP 50–63 spreading determinant. Our results suggest that self-presentation by HLA-DP may play an important role in epitope spreading and in the propagation of self-recognition during the clinical progression of MS.</div></front></TEI><istex><corpusName>elsevier</corpusName><keywords><teeft><json:string>myelin</json:string><json:string>multiple sclerosis</json:string><json:string>allele</json:string><json:string>peptide</json:string><json:string>imds</json:string><json:string>sclerosis</json:string><json:string>epitope</json:string><json:string>immunol</json:string><json:string>cell lines</json:string><json:string>proteolipid</json:string><json:string>haplotype</json:string><json:string>determinant</json:string><json:string>pbmc</json:string><json:string>neurologic</json:string><json:string>lysis</json:string><json:string>myelin proteolipid protein</json:string><json:string>imds patients</json:string><json:string>multiple sclerosis patients</json:string><json:string>neuroimmunol</json:string><json:string>proliferative</json:string><json:string>autoreactivity</json:string><json:string>present study</json:string><json:string>control subjects</json:string><json:string>early stages</json:string><json:string>cleveland clinic foundation</json:string><json:string>proliferative responses</json:string><json:string>human immunol</json:string><json:string>neurologic symptoms</json:string><json:string>target cell lysis</json:string><json:string>becton dickinson</json:string><json:string>peptide series</json:string><json:string>tuohy</json:string><json:string>initial onset</json:string><json:string>total volume</json:string><json:string>control wells</json:string><json:string>myelin proteins</json:string><json:string>control peptide</json:string><json:string>cell recognition</json:string><json:string>cell responses</json:string><json:string>restriction element</json:string><json:string>study subjects</json:string><json:string>disease outcome</json:string><json:string>stimulation index</json:string><json:string>tissue antigens</json:string><json:string>susceptibility</json:string><json:string>imds subjects</json:string><json:string>complete disparity</json:string><json:string>disease risk</json:string><json:string>microtiter falcon plates</json:string><json:string>early development</json:string><json:string>glass fiber filters</json:string><json:string>scintillation spectrometry</json:string><json:string>important role</json:string><json:string>clinical progression</json:string><json:string>myelin oligodendrocyte glycoprotein</json:string><json:string>hepes buffer</json:string><json:string>human immunology</json:string><json:string>several reports</json:string><json:string>tetanus toxoid</json:string><json:string>mycobacteria tuberculosis</json:string><json:string>linkage disequilibrium</json:string><json:string>falcon plates</json:string><json:string>autologous serum</json:string><json:string>european collection</json:string><json:string>animal cell cultures</json:string><json:string>target cells</json:string><json:string>american society</json:string><json:string>total incorporation</json:string><json:string>clinical course</json:string><json:string>specific lysis</json:string><json:string>spontaneous release</json:string><json:string>month period</json:string><json:string>elsevier science</json:string><json:string>cervical myelitis</json:string><json:string>monosymptomatic demyelination syndromes</json:string><json:string>variable rates</json:string><json:string>encephalitogenic determinant</json:string><json:string>dual restriction</json:string><json:string>risk factor</json:string><json:string>systemic sclerosis</json:string><json:string>permissive alleles</json:string><json:string>homozygous typing</json:string><json:string>extensive plasticity</json:string><json:string>restriction molecule</json:string><json:string>study protocol</json:string><json:string>immunodominant myelin</json:string><json:string>proc natl acad</json:string><json:string>fine specificity</json:string><json:string>cell response</json:string><json:string>protein peptide</json:string><json:string>cerebrospinal fluid</json:string><json:string>cell epitope</json:string><json:string>proteolipid protein</json:string><json:string>molecular analysis</json:string><json:string>amino acid</json:string></teeft></keywords><author><json:item><name>Min Yu</name><affiliations><json:string>Department of Immunology, The Cleveland Clinic Foundation, Cleveland, OH, 44195, USA (M.Y., V.K.T.),</json:string></affiliations></json:item><json:item><name>R.Philip Kinkel</name><affiliations><json:string>Mellen Center for Multiple Sclerosis Research and Treatment (R.P.K., B.W.G., V.K.T.), The Cleveland Clinic Foundation, Cleveland, OH, 44195, USA,</json:string></affiliations></json:item><json:item><name>Bianca Weinstock-Guttman</name><affiliations><json:string>Mellen Center for Multiple Sclerosis Research and Treatment (R.P.K., B.W.G., V.K.T.), The Cleveland Clinic Foundation, Cleveland, OH, 44195, USA,</json:string></affiliations></json:item><json:item><name>Daniel J. Cook</name><affiliations><json:string>Histocompatibility Laboratory (D.J.C.), The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.</json:string></affiliations></json:item><json:item><name>Vincent K. Tuohy</name><affiliations><json:string>Department of Immunology, The Cleveland Clinic Foundation, Cleveland, OH, 44195, USA (M.Y., V.K.T.),</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>CNS : central nervous system</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>EAE : experimental autoimmune encephalomyelitis</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>FMOC : 9-Fluorenylmethoxycarbonyl-</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>HPLC : high pressure liquid chromatography</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>HTC : homozygous typing B cells</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>IMDS : isolated monosymptomatic demyelinating syndromes</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>MAG : myelin associated glycoprotein</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>MBP : myelin basic protein</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>MOG : myelin oligodendrocyte glycoprotein</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>MRI : magnetic resonance imaging</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>MS : multiple sclerosis</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>OND : other neurologic diseases</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>PBMC : peripheral blood mononuclear cells</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>PCR-SSOP : polymerase chain reaction-sequence specific oligonucleotide probe typing</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>PLP : myelin proteolipid protein</value></json:item></subject><arkIstex>ark:/67375/6H6-80VHPCL3-S</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>Full-length article</json:string></originalGenre><abstract>Abstract: ABSTRACT: Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system. It is widely believed that complex polygenic inheritance patterns involving HLA-DR and -DQ class II genes contribute to MS susceptibility, and current evidence indicates that disease risk vs disease outcome may be associated with distinctly different HLA class II alleles. We have recently shown that the early development of MS is accompanied by an extensive plasticity of myelin self-recognition with the acquisition of neo-autoreactivity, or epitope spreading, as a prominent feature. Although we did not observe a common determinant recognized by patients sharing identical HLA-DR or -DQ class II alleles, we did observe epitope spreading to the p50–63 determinant of myelin proteolipid protein (PLP) in two study subjects showing complete disparity at HLA-DR and -DQ but identity at the HLA-DP allele DPB1∗0301. In the present study we show that self-recognition during the early stages in the development of MS involves HLA-DP class II restricted responses to the PLP 50–63 spreading determinant. Our results suggest that self-presentation by HLA-DP may play an important role in epitope spreading and in the propagation of self-recognition during the clinical progression of MS.</abstract><qualityIndicators><score>9.316</score><pdfWordCount>5402</pdfWordCount><pdfCharCount>35042</pdfCharCount><pdfVersion>1.2</pdfVersion><pdfPageCount>10</pdfPageCount><pdfPageSize>596 x 794 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractWordCount>193</abstractWordCount><abstractCharCount>1299</abstractCharCount><keywordCount>15</keywordCount></qualityIndicators><title>HLA-DP: A Class II Restriction Molecule Involved in Epitope Spreading During the Development of Multiple Sclerosis</title><pmid><json:string>9544235</json:string></pmid><pii><json:string>S0198-8859(97)00252-8</json:string></pii><genre><json:string>research-article</json:string></genre><host><title>Human Immunology</title><language><json:string>unknown</json:string></language><publicationDate>1998</publicationDate><issn><json:string>0198-8859</json:string></issn><pii><json:string>S0198-8859(00)X0036-5</json:string></pii><volume>59</volume><issue>1</issue><pages><first>15</first><last>24</last></pages><genre><json:string>journal</json:string></genre></host><namedEntities><unitex><date><json:string>1998</json:string></date><geogName></geogName><orgName><json:string>Cleveland Clinic Foundation</json:string><json:string>Elsevier Science Inc</json:string><json:string>Lederle Laboratories</json:string><json:string>Biotech</json:string><json:string>Internal Review Board of the Cleveland Clinic Foundation</json:string><json:string>Difco Laboratories, Detroit</json:string><json:string>National Institutes of Health</json:string><json:string>Biotech, Uppsala, Sweden</json:string><json:string>Mimotopes</json:string><json:string>National Multiple Sclerosis Society grant RG2768</json:string><json:string>V.K.T.</json:string></orgName><orgName_funder><json:string>National Multiple Sclerosis Society grant RG2768</json:string><json:string>V.K.T.</json:string></orgName_funder><orgName_provider></orgName_provider><persName><json:string>R. Philip</json:string><json:string>Franklin Lakes</json:string><json:string>Pearl River</json:string><json:string>The</json:string><json:string>Human Immunology</json:string><json:string>Daniel J. Cook</json:string><json:string>Bianca Weinstock-Guttman</json:string></persName><placeName><json:string>Cytotoxicity</json:string><json:string>UK</json:string><json:string>Washington</json:string><json:string>Ulvestad</json:string><json:string>Boston</json:string><json:string>Raritan</json:string><json:string>CA</json:string><json:string>MA</json:string><json:string>NJ</json:string><json:string>PA</json:string></placeName><ref_url></ref_url><ref_bibl><json:string>[45]</json:string><json:string>[15, 41, 42]</json:string><json:string>[44]</json:string><json:string>[21, 22]</json:string><json:string>[39]</json:string><json:string>[21]</json:string><json:string>[39, 40]</json:string><json:string>[49]</json:string><json:string>M. Yu et al.</json:string><json:string>[50, 51]</json:string><json:string>[53]</json:string><json:string>[1, 2]</json:string><json:string>Histocompatibility and Immunogenetics, 1998</json:string><json:string>[48]</json:string><json:string>[52]</json:string><json:string>[47]</json:string><json:string>[46]</json:string></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/6H6-80VHPCL3-S</json:string></ark><categories><wos><json:string>1 - science</json:string><json:string>2 - immunology</json:string></wos><scienceMetrix><json:string>1 - health sciences</json:string><json:string>2 - clinical medicine</json:string><json:string>3 - immunology</json:string></scienceMetrix><scopus><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - General Medicine</json:string><json:string>1 - Life Sciences</json:string><json:string>2 - Immunology and Microbiology</json:string><json:string>3 - Immunology</json:string><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - Immunology and Allergy</json:string></scopus><inist><json:string>1 - sciences appliquees, technologies et medecines</json:string><json:string>2 - sciences biologiques et medicales</json:string><json:string>3 - sciences medicales</json:string></inist></categories><publicationDate>1998</publicationDate><copyrightDate>1998</copyrightDate><doi><json:string>10.1016/S0198-8859(97)00252-8</json:string></doi><id>9D16647DA0308237F9397AE0BC33DB40122A26FE</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-80VHPCL3-S/fulltext.pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-80VHPCL3-S/bundle.zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/ark:/67375/6H6-80VHPCL3-S/fulltext.tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">HLA-DP: A Class II Restriction Molecule Involved in Epitope Spreading During the Development of Multiple Sclerosis</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher scheme="https://scientific-publisher.data.istex.fr">ELSEVIER</publisher><availability><licence><p>©1998 American Society for Histocompatibility and Immunogenetics</p></licence><p scheme="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-HKKZVM7B-M">elsevier</p></availability><date>1998</date></publicationStmt><notesStmt><note type="research-article" scheme="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</note><note type="journal" scheme="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</note><note type="content">Section title: miscellaneous</note><note type="content">Fig. 1: Epitope-Mapping Peptide Series For PLP. An overlapping series of 12-mer peptides effectively representing a walk-through of the entire 276 amino acid primary sequence of mouse PLP was used in serial evaluation of proliferative responses of PBMC from IMDS patients and controls.</note><note type="content">Fig. 2: Anti-DP Mediated Inhibiton Of Autoreactive CD4+ T Cell Lines. CD4+ T cell lines specific for PLP 43-64 were generated from VS and SW. Proliferative responses to PLP 43-64 were tested in the presence of 1.0 μg/ml mAb specific for HLA-DR, -DQ, or -DP. Antigen-specific proliferation of T cell lines was inhibited only in the presence of mAb specific for HLA-DP. Mean background counts were ⩽3,000 cpm.</note><note type="content">Fig. 3: HLA-DP Mediated Target Cell Lysis By Autoreactive CD4+ T Cell Lines. PLP 43-64 specific CD4+ T cell lines from VS and SW were tested for their ability to lyse EBV-transformed homozygous typing B cells (HTC) with defined HLA haplotypes (Table 2). Antigen-specific lysis was directed only against IHW9018 cells, an HTC line showing class II compatibility with VS and SW only at the DPB1∗0301 allele (Table 2).</note><note type="content">Table 1: Serial PBMC Responses to PLP Peptides by IMDS Patientsa</note><note type="content">Table 2: HLA-DR/DQ/DP Haplotypes of IMDS Patientsa and Homozygous Typing Cell Lines (HTC)b</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">HLA-DP: A Class II Restriction Molecule Involved in Epitope Spreading During the Development of Multiple Sclerosis</title><author xml:id="author-0000"><persName><forename type="first">Min</forename><surname>Yu</surname></persName><affiliation>Department of Immunology, The Cleveland Clinic Foundation, Cleveland, OH, 44195, USA (M.Y., V.K.T.),</affiliation></author><author xml:id="author-0001"><persName><forename type="first">R.Philip</forename><surname>Kinkel</surname></persName><affiliation>Mellen Center for Multiple Sclerosis Research and Treatment (R.P.K., B.W.G., V.K.T.), The Cleveland Clinic Foundation, Cleveland, OH, 44195, USA,</affiliation></author><author xml:id="author-0002"><persName><forename type="first">Bianca</forename><surname>Weinstock-Guttman</surname></persName><affiliation>Mellen Center for Multiple Sclerosis Research and Treatment (R.P.K., B.W.G., V.K.T.), The Cleveland Clinic Foundation, Cleveland, OH, 44195, USA,</affiliation></author><author xml:id="author-0003"><persName><forename type="first">Daniel J.</forename><surname>Cook</surname></persName><affiliation>Histocompatibility Laboratory (D.J.C.), The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.</affiliation></author><author xml:id="author-0004"><persName><forename type="first">Vincent K.</forename><surname>Tuohy</surname></persName><note type="biography">Dr. Vincent K. Tuohy, The Cleveland Clinic Foundation, Department of Immunology, FFb-1, 9500 Euclid Avenue, Cleveland, OH 44195, USA; Tel: (216) 445-9684; Fax: (216) 444-8372; E-Mail: tuohyv@cesmtp.ccf.org.</note><affiliation>Dr. Vincent K. Tuohy, The Cleveland Clinic Foundation, Department of Immunology, FFb-1, 9500 Euclid Avenue, Cleveland, OH 44195, USA; Tel: (216) 445-9684; Fax: (216) 444-8372; E-Mail: tuohyv@cesmtp.ccf.org.</affiliation><affiliation>Department of Immunology, The Cleveland Clinic Foundation, Cleveland, OH, 44195, USA (M.Y., V.K.T.),</affiliation></author><idno type="istex">9D16647DA0308237F9397AE0BC33DB40122A26FE</idno><idno type="ark">ark:/67375/6H6-80VHPCL3-S</idno><idno type="DOI">10.1016/S0198-8859(97)00252-8</idno><idno type="PII">S0198-8859(97)00252-8</idno></analytic><monogr><title level="j">Human Immunology</title><title level="j" type="abbrev">HIM</title><idno type="pISSN">0198-8859</idno><idno type="PII">S0198-8859(00)X0036-5</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1998"></date><biblScope unit="volume">59</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="15">15</biblScope><biblScope unit="page" to="24">24</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1998</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Abstract: ABSTRACT: Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system. It is widely believed that complex polygenic inheritance patterns involving HLA-DR and -DQ class II genes contribute to MS susceptibility, and current evidence indicates that disease risk vs disease outcome may be associated with distinctly different HLA class II alleles. We have recently shown that the early development of MS is accompanied by an extensive plasticity of myelin self-recognition with the acquisition of neo-autoreactivity, or epitope spreading, as a prominent feature. Although we did not observe a common determinant recognized by patients sharing identical HLA-DR or -DQ class II alleles, we did observe epitope spreading to the p50–63 determinant of myelin proteolipid protein (PLP) in two study subjects showing complete disparity at HLA-DR and -DQ but identity at the HLA-DP allele DPB1∗0301. In the present study we show that self-recognition during the early stages in the development of MS involves HLA-DP class II restricted responses to the PLP 50–63 spreading determinant. Our results suggest that self-presentation by HLA-DP may play an important role in epitope spreading and in the propagation of self-recognition during the clinical progression of MS.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Abbreviations</head><item><term>CNS</term><term>central nervous system</term></item><item><term>EAE</term><term>experimental autoimmune encephalomyelitis</term></item><item><term>FMOC</term><term>9-Fluorenylmethoxycarbonyl-</term></item><item><term>HPLC</term><term>high pressure liquid chromatography</term></item><item><term>HTC</term><term>homozygous typing B cells</term></item><item><term>IMDS</term><term>isolated monosymptomatic demyelinating syndromes</term></item><item><term>MAG</term><term>myelin associated glycoprotein</term></item><item><term>MBP</term><term>myelin basic protein</term></item><item><term>MOG</term><term>myelin oligodendrocyte glycoprotein</term></item><item><term>MRI</term><term>magnetic resonance imaging</term></item><item><term>MS</term><term>multiple sclerosis</term></item><item><term>OND</term><term>other neurologic diseases</term></item><item><term>PBMC</term><term>peripheral blood mononuclear cells</term></item><item><term>PCR-SSOP</term><term>polymerase chain reaction-sequence specific oligonucleotide probe typing</term></item><item><term>PLP</term><term>myelin proteolipid protein</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="1997-11-13">Modified</change><change when="1998">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-80VHPCL3-S/fulltext.txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier, elements deleted: ce:floats; body; tail"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 4.5.2//EN//XML" URI="art452.dtd" name="istex:docType"><istex:entity SYSTEM="gr1" NDATA="IMAGE" name="gr1"></istex:entity><istex:entity SYSTEM="gr2" NDATA="IMAGE" name="gr2"></istex:entity><istex:entity SYSTEM="gr3" NDATA="IMAGE" name="gr3"></istex:entity></istex:docType><istex:document><converted-article version="4.5.2" docsubtype="fla" xml:lang="en"><item-info><jid>HIM</jid><aid>5228</aid><ce:pii>S0198-8859(97)00252-8</ce:pii><ce:doi>10.1016/S0198-8859(97)00252-8</ce:doi><ce:copyright year="1998" type="society">American Society for Histocompatibility and Immunogenetics</ce:copyright></item-info><head><ce:dochead><ce:textfn>miscellaneous</ce:textfn></ce:dochead><ce:title>HLA-DP: A Class II Restriction Molecule Involved in Epitope Spreading During the Development of Multiple Sclerosis</ce:title><ce:author-group><ce:author><ce:indexed-name>Yu</ce:indexed-name><ce:given-name>Min</ce:given-name><ce:surname>Yu</ce:surname><ce:cross-ref refid="AFF1">A</ce:cross-ref></ce:author><ce:author><ce:indexed-name>Kinkel</ce:indexed-name><ce:given-name>R.Philip</ce:given-name><ce:surname>Kinkel</ce:surname><ce:cross-ref refid="AFF2">B</ce:cross-ref></ce:author><ce:author><ce:indexed-name>Weinstock-Guttman</ce:indexed-name><ce:given-name>Bianca</ce:given-name><ce:surname>Weinstock-Guttman</ce:surname><ce:cross-ref refid="AFF2">B</ce:cross-ref></ce:author><ce:author><ce:indexed-name>Cook</ce:indexed-name><ce:given-name>Daniel J.</ce:given-name><ce:surname>Cook</ce:surname><ce:cross-ref refid="AFF3">C</ce:cross-ref></ce:author><ce:author><ce:indexed-name>Tuohy</ce:indexed-name><ce:given-name>Vincent K.</ce:given-name><ce:surname>Tuohy</ce:surname><ce:cross-ref refid="AFF1">A</ce:cross-ref><ce:cross-ref refid="AFF2">B</ce:cross-ref><ce:cross-ref refid="CORR1">*</ce:cross-ref></ce:author><ce:affiliation id="AFF1"><ce:label>A</ce:label><ce:textfn>Department of Immunology, The Cleveland Clinic Foundation, Cleveland, OH, 44195, USA (M.Y., V.K.T.),</ce:textfn></ce:affiliation><ce:affiliation id="AFF2"><ce:label>B</ce:label><ce:textfn>Mellen Center for Multiple Sclerosis Research and Treatment (R.P.K., B.W.G., V.K.T.), The Cleveland Clinic Foundation, Cleveland, OH, 44195, USA,</ce:textfn></ce:affiliation><ce:affiliation id="AFF3"><ce:label>C</ce:label><ce:textfn>Histocompatibility Laboratory (D.J.C.), The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.</ce:textfn></ce:affiliation><ce:correspondence id="CORR1"><ce:label>*</ce:label><ce:text>Dr. Vincent K. Tuohy, The Cleveland Clinic Foundation, Department of Immunology, FFb-1, 9500 Euclid Avenue, Cleveland, OH 44195, USA; Tel: (216) 445-9684; Fax: (216) 444-8372; E-Mail: tuohyv@cesmtp.ccf.org.</ce:text></ce:correspondence></ce:author-group><ce:date-received day="22" month="8" year="1997"></ce:date-received><ce:date-revised day="13" month="11" year="1997"></ce:date-revised><ce:date-accepted day="18" month="11" year="1997"></ce:date-accepted><ce:abstract><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para>ABSTRACT: Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system. It is widely believed that complex polygenic inheritance patterns involving HLA-DR and -DQ class II genes contribute to MS susceptibility, and current evidence indicates that disease risk vs disease outcome may be associated with distinctly different HLA class II alleles. We have recently shown that the early development of MS is accompanied by an extensive plasticity of myelin self-recognition with the acquisition of neo-autoreactivity, or epitope spreading, as a prominent feature. Although we did not observe a common determinant recognized by patients sharing identical HLA-DR or -DQ class II alleles, we did observe epitope spreading to the p50–63 determinant of myelin proteolipid protein (PLP) in two study subjects showing complete disparity at HLA-DR and -DQ but identity at the HLA-DP allele DPB1∗0301. In the present study we show that self-recognition during the early stages in the development of MS involves HLA-DP class II restricted responses to the PLP 50–63 spreading determinant. Our results suggest that self-presentation by HLA-DP may play an important role in epitope spreading and in the propagation of self-recognition during the clinical progression of MS.</ce:simple-para></ce:abstract-sec></ce:abstract><ce:keywords class="abr"><ce:section-title>Abbreviations</ce:section-title><ce:keyword><ce:text>CNS</ce:text><ce:keyword><ce:text>central nervous system</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>EAE</ce:text><ce:keyword><ce:text>experimental autoimmune encephalomyelitis</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>FMOC</ce:text><ce:keyword><ce:text>9-Fluorenylmethoxycarbonyl-</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>HPLC</ce:text><ce:keyword><ce:text>high pressure liquid chromatography</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>HTC</ce:text><ce:keyword><ce:text>homozygous typing B cells</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>IMDS</ce:text><ce:keyword><ce:text>isolated monosymptomatic demyelinating syndromes</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>MAG</ce:text><ce:keyword><ce:text>myelin associated glycoprotein</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>MBP</ce:text><ce:keyword><ce:text>myelin basic protein</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>MOG</ce:text><ce:keyword><ce:text>myelin oligodendrocyte glycoprotein</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>MRI</ce:text><ce:keyword><ce:text>magnetic resonance imaging</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>MS</ce:text><ce:keyword><ce:text>multiple sclerosis</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>OND</ce:text><ce:keyword><ce:text>other neurologic diseases</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>PBMC</ce:text><ce:keyword><ce:text>peripheral blood mononuclear cells</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>PCR-SSOP</ce:text><ce:keyword><ce:text>polymerase chain reaction-sequence specific oligonucleotide probe typing</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>PLP</ce:text><ce:keyword><ce:text>myelin proteolipid protein</ce:text></ce:keyword></ce:keyword></ce:keywords></head></converted-article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>HLA-DP: A Class II Restriction Molecule Involved in Epitope Spreading During the Development of Multiple Sclerosis</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>HLA-DP: A Class II Restriction Molecule Involved in Epitope Spreading During the Development of Multiple Sclerosis</title></titleInfo><name type="personal"><namePart type="given">Min</namePart><namePart type="family">Yu</namePart><affiliation>Department of Immunology, The Cleveland Clinic Foundation, Cleveland, OH, 44195, USA (M.Y., V.K.T.),</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">R.Philip</namePart><namePart type="family">Kinkel</namePart><affiliation>Mellen Center for Multiple Sclerosis Research and Treatment (R.P.K., B.W.G., V.K.T.), The Cleveland Clinic Foundation, Cleveland, OH, 44195, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Bianca</namePart><namePart type="family">Weinstock-Guttman</namePart><affiliation>Mellen Center for Multiple Sclerosis Research and Treatment (R.P.K., B.W.G., V.K.T.), The Cleveland Clinic Foundation, Cleveland, OH, 44195, USA,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Daniel J.</namePart><namePart type="family">Cook</namePart><affiliation>Histocompatibility Laboratory (D.J.C.), The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Vincent K.</namePart><namePart type="family">Tuohy</namePart><affiliation>Department of Immunology, The Cleveland Clinic Foundation, Cleveland, OH, 44195, USA (M.Y., V.K.T.),</affiliation><description>Dr. Vincent K. Tuohy, The Cleveland Clinic Foundation, Department of Immunology, FFb-1, 9500 Euclid Avenue, Cleveland, OH 44195, USA; Tel: (216) 445-9684; Fax: (216) 444-8372; E-Mail: tuohyv@cesmtp.ccf.org.</description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1998</dateIssued><dateModified encoding="w3cdtf">1997-11-13</dateModified><copyrightDate encoding="w3cdtf">1998</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><abstract lang="en">Abstract: ABSTRACT: Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system. It is widely believed that complex polygenic inheritance patterns involving HLA-DR and -DQ class II genes contribute to MS susceptibility, and current evidence indicates that disease risk vs disease outcome may be associated with distinctly different HLA class II alleles. We have recently shown that the early development of MS is accompanied by an extensive plasticity of myelin self-recognition with the acquisition of neo-autoreactivity, or epitope spreading, as a prominent feature. Although we did not observe a common determinant recognized by patients sharing identical HLA-DR or -DQ class II alleles, we did observe epitope spreading to the p50–63 determinant of myelin proteolipid protein (PLP) in two study subjects showing complete disparity at HLA-DR and -DQ but identity at the HLA-DP allele DPB1∗0301. In the present study we show that self-recognition during the early stages in the development of MS involves HLA-DP class II restricted responses to the PLP 50–63 spreading determinant. Our results suggest that self-presentation by HLA-DP may play an important role in epitope spreading and in the propagation of self-recognition during the clinical progression of MS.</abstract><note type="content">Section title: miscellaneous</note><note type="content">Fig. 1: Epitope-Mapping Peptide Series For PLP. An overlapping series of 12-mer peptides effectively representing a walk-through of the entire 276 amino acid primary sequence of mouse PLP was used in serial evaluation of proliferative responses of PBMC from IMDS patients and controls.</note><note type="content">Fig. 2: Anti-DP Mediated Inhibiton Of Autoreactive CD4+ T Cell Lines. CD4+ T cell lines specific for PLP 43-64 were generated from VS and SW. Proliferative responses to PLP 43-64 were tested in the presence of 1.0 μg/ml mAb specific for HLA-DR, -DQ, or -DP. Antigen-specific proliferation of T cell lines was inhibited only in the presence of mAb specific for HLA-DP. Mean background counts were ⩽3,000 cpm.</note><note type="content">Fig. 3: HLA-DP Mediated Target Cell Lysis By Autoreactive CD4+ T Cell Lines. PLP 43-64 specific CD4+ T cell lines from VS and SW were tested for their ability to lyse EBV-transformed homozygous typing B cells (HTC) with defined HLA haplotypes (Table 2). Antigen-specific lysis was directed only against IHW9018 cells, an HTC line showing class II compatibility with VS and SW only at the DPB1∗0301 allele (Table 2).</note><note type="content">Table 1: Serial PBMC Responses to PLP Peptides by IMDS Patientsa</note><note type="content">Table 2: HLA-DR/DQ/DP Haplotypes of IMDS Patientsa and Homozygous Typing Cell Lines (HTC)b</note><subject lang="en"><genre>Abbreviations</genre><topic>CNS : central nervous system</topic><topic>EAE : experimental autoimmune encephalomyelitis</topic><topic>FMOC : 9-Fluorenylmethoxycarbonyl-</topic><topic>HPLC : high pressure liquid chromatography</topic><topic>HTC : homozygous typing B cells</topic><topic>IMDS : isolated monosymptomatic demyelinating syndromes</topic><topic>MAG : myelin associated glycoprotein</topic><topic>MBP : myelin basic protein</topic><topic>MOG : myelin oligodendrocyte glycoprotein</topic><topic>MRI : magnetic resonance imaging</topic><topic>MS : multiple sclerosis</topic><topic>OND : other neurologic diseases</topic><topic>PBMC : peripheral blood mononuclear cells</topic><topic>PCR-SSOP : polymerase chain reaction-sequence specific oligonucleotide probe typing</topic><topic>PLP : myelin proteolipid protein</topic></subject><relatedItem type="host"><titleInfo><title>Human Immunology</title></titleInfo><titleInfo type="abbreviated"><title>HIM</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1998</dateIssued></originInfo><identifier type="ISSN">0198-8859</identifier><identifier type="PII">S0198-8859(00)X0036-5</identifier><part><date>1998</date><detail type="volume"><number>59</number><caption>vol.</caption></detail><detail type="issue"><number>1</number><caption>no.</caption></detail><extent unit="issue-pages"><start>1</start><end>70</end></extent><extent unit="pages"><start>15</start><end>24</end></extent></part></relatedItem><identifier type="istex">9D16647DA0308237F9397AE0BC33DB40122A26FE</identifier><identifier type="ark">ark:/67375/6H6-80VHPCL3-S</identifier><identifier type="DOI">10.1016/S0198-8859(97)00252-8</identifier><identifier type="PII">S0198-8859(97)00252-8</identifier><accessCondition type="use and reproduction" contentType="copyright">©1998 American Society for Histocompatibility and Immunogenetics</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-HKKZVM7B-M">elsevier</recordContentSource><recordOrigin>American Society for Histocompatibility and Immunogenetics, ©1998</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-80VHPCL3-S/record.json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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