Synthetic peptides that inhibit binding of the myelin basic protein 85-99 epitope to multiple sclerosis-associated HLA-DR2 molecules and MBP-specific T-cell responses
Identifieur interne : 000819 ( Istex/Corpus ); précédent : 000818; suivant : 000820Synthetic peptides that inhibit binding of the myelin basic protein 85-99 epitope to multiple sclerosis-associated HLA-DR2 molecules and MBP-specific T-cell responses
Auteurs : Masha Fridkis-Hareli ; Joel N. H Stern ; Lars Fugger ; Jack L. StromingerSource :
- Human Immunology [ 0198-8859 ] ; 2001.
English descriptors
- KwdEn :
- Teeft :
- Acad, Amino acids, Antigen presentation, Arnon, Assay, Binding motif, Binding motifs, Biotinylated, Cell clones, Clone, Copolymer, Crystal structure, Encephalomyelitis, Epitope, Final peptide concentration, Hafler, Histocompatibility, Hy1b, Immunodominant, Immunodominant epitope, Immunodominant myelin, Immunol, Inhibitor, Major histocompatibility, Methods section, Molecule, Multiple sclerosis, Myelin, Natl, Peptide, Polyclonal antibodies, Proc, Proc natl acad, Protein peptide, Random polypeptides, Sclerosis, Sela, Several peptides, Side chains, Sodium chloride, Strominger, Synthetic peptides, Teitelbaum, Unlabeled, Wucherpfennig.
Abstract
Abstract: Copolymer 1 (Cop 1, poly [Y, E, A, K]) is a random synthetic amino acid copolymer effective in the treatment of relapsing forms of multiple sclerosis (MS), a disease that is linked to HLA-DR2 (DRB1∗1501). In the present study various peptides, synthesized according to the binding motifs for both the immunodominant epitope of myelin basic protein (MBP) 85-99, a candidate autoantigen in MS, and Cop 1, differentially inhibited binding of these antigens to disease-associated HLA-DR2 (DRB1∗1501) molecules. In particular, two peptides with residue K at position P-1, as referred to MBP 85-99, inhibited effectively the binding of both biotinylated MBP 85-99 and Cop 1 to HLA-DR2 molecules as well as IL-2 production by two MBP-specific HLA-DR2-restricted T-cell clones. These findings suggest the possible utility of these compounds or their more stable derivatives in treatment of MS.
Url:
DOI: 10.1016/S0198-8859(01)00279-8
Links to Exploration step
ISTEX:0575E1F655B214465309154DC12F7A6C8421EFC7Le document en format XML
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H Stern</name><affiliation><mods:affiliation>Department of Molecular and Cellular Biology (M.F.-H., J.N.H.S., J.L.S.), Harvard University, Cambridge, MA, USA</mods:affiliation></affiliation></author><author><name sortKey="Fugger, Lars" sort="Fugger, Lars" uniqKey="Fugger L" first="Lars" last="Fugger">Lars Fugger</name><affiliation><mods:affiliation>Department of Clinical Immunology (L. F.), Aarhus University Hospital, Skejby Sygehus, Aarhus N, Denmark</mods:affiliation></affiliation></author><author><name sortKey="Strominger, Jack L" sort="Strominger, Jack L" uniqKey="Strominger J" first="Jack L" last="Strominger">Jack L. 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H" last="Stern">Joel N. H Stern</name><affiliation><mods:affiliation>Department of Molecular and Cellular Biology (M.F.-H., J.N.H.S., J.L.S.), Harvard University, Cambridge, MA, USA</mods:affiliation></affiliation></author><author><name sortKey="Fugger, Lars" sort="Fugger, Lars" uniqKey="Fugger L" first="Lars" last="Fugger">Lars Fugger</name><affiliation><mods:affiliation>Department of Clinical Immunology (L. F.), Aarhus University Hospital, Skejby Sygehus, Aarhus N, Denmark</mods:affiliation></affiliation></author><author><name sortKey="Strominger, Jack L" sort="Strominger, Jack L" uniqKey="Strominger J" first="Jack L" last="Strominger">Jack L. Strominger</name><affiliation><mods:affiliation>E-mail: jlstrom@fas.harvard.edu</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Molecular and Cellular Biology (M.F.-H., J.N.H.S., J.L.S.), Harvard University, Cambridge, MA, USA</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="2001">2001</date><biblScope unit="volume">62</biblScope><biblScope unit="issue">8</biblScope><biblScope unit="page" from="753">753</biblScope><biblScope unit="page" to="763">763</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>Cop 1</term><term>HA</term><term>HLA-DR</term><term>MBP</term><term>MS</term><term>RA</term><term>T cells</term><term>peptides</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Acad</term><term>Amino acids</term><term>Antigen presentation</term><term>Arnon</term><term>Assay</term><term>Binding motif</term><term>Binding motifs</term><term>Biotinylated</term><term>Cell clones</term><term>Clone</term><term>Copolymer</term><term>Crystal structure</term><term>Encephalomyelitis</term><term>Epitope</term><term>Final peptide concentration</term><term>Hafler</term><term>Histocompatibility</term><term>Hy1b</term><term>Immunodominant</term><term>Immunodominant epitope</term><term>Immunodominant myelin</term><term>Immunol</term><term>Inhibitor</term><term>Major histocompatibility</term><term>Methods section</term><term>Molecule</term><term>Multiple sclerosis</term><term>Myelin</term><term>Natl</term><term>Peptide</term><term>Polyclonal antibodies</term><term>Proc</term><term>Proc natl acad</term><term>Protein peptide</term><term>Random polypeptides</term><term>Sclerosis</term><term>Sela</term><term>Several peptides</term><term>Side chains</term><term>Sodium chloride</term><term>Strominger</term><term>Synthetic peptides</term><term>Teitelbaum</term><term>Unlabeled</term><term>Wucherpfennig</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: Copolymer 1 (Cop 1, poly [Y, E, A, K]) is a random synthetic amino acid copolymer effective in the treatment of relapsing forms of multiple sclerosis (MS), a disease that is linked to HLA-DR2 (DRB1∗1501). In the present study various peptides, synthesized according to the binding motifs for both the immunodominant epitope of myelin basic protein (MBP) 85-99, a candidate autoantigen in MS, and Cop 1, differentially inhibited binding of these antigens to disease-associated HLA-DR2 (DRB1∗1501) molecules. In particular, two peptides with residue K at position P-1, as referred to MBP 85-99, inhibited effectively the binding of both biotinylated MBP 85-99 and Cop 1 to HLA-DR2 molecules as well as IL-2 production by two MBP-specific HLA-DR2-restricted T-cell clones. These findings suggest the possible utility of these compounds or their more stable derivatives in treatment of MS.</div></front></TEI><istex><corpusName>elsevier</corpusName><keywords><teeft><json:string>peptide</json:string><json:string>synthetic peptides</json:string><json:string>biotinylated</json:string><json:string>copolymer</json:string><json:string>epitope</json:string><json:string>myelin</json:string><json:string>clone</json:string><json:string>immunol</json:string><json:string>strominger</json:string><json:string>multiple sclerosis</json:string><json:string>immunodominant</json:string><json:string>hafler</json:string><json:string>hy1b</json:string><json:string>wucherpfennig</json:string><json:string>teitelbaum</json:string><json:string>sela</json:string><json:string>arnon</json:string><json:string>encephalomyelitis</json:string><json:string>sclerosis</json:string><json:string>histocompatibility</json:string><json:string>unlabeled</json:string><json:string>proc</json:string><json:string>natl</json:string><json:string>acad</json:string><json:string>proc natl acad</json:string><json:string>crystal structure</json:string><json:string>cell clones</json:string><json:string>assay</json:string><json:string>binding motifs</json:string><json:string>several peptides</json:string><json:string>major histocompatibility</json:string><json:string>polyclonal antibodies</json:string><json:string>binding motif</json:string><json:string>immunodominant epitope</json:string><json:string>molecule</json:string><json:string>immunodominant myelin</json:string><json:string>protein peptide</json:string><json:string>sodium chloride</json:string><json:string>antigen presentation</json:string><json:string>final peptide concentration</json:string><json:string>side chains</json:string><json:string>amino acids</json:string><json:string>methods section</json:string><json:string>random polypeptides</json:string><json:string>inhibitor</json:string></teeft></keywords><author><json:item><name>Masha Fridkis-Hareli</name><affiliations><json:string>Department of Molecular and Cellular Biology (M.F.-H., J.N.H.S., J.L.S.), Harvard University, Cambridge, MA, USA</json:string></affiliations></json:item><json:item><name>Joel N.H Stern</name><affiliations><json:string>Department of Molecular and Cellular Biology (M.F.-H., J.N.H.S., J.L.S.), Harvard University, Cambridge, MA, USA</json:string></affiliations></json:item><json:item><name>Lars Fugger</name><affiliations><json:string>Department of Clinical Immunology (L. F.), Aarhus University Hospital, Skejby Sygehus, Aarhus N, Denmark</json:string></affiliations></json:item><json:item><name>Jack L Strominger</name><affiliations><json:string>E-mail: jlstrom@fas.harvard.edu</json:string><json:string>Department of Molecular and Cellular Biology (M.F.-H., J.N.H.S., J.L.S.), Harvard University, Cambridge, MA, USA</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>MS</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>MBP</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>HLA-DR</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Cop 1</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>T cells</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>peptides</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Cop 1 : copolymer 1</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>HA : influenza virus hemagglutinin</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>MS : multiple sclerosis</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>RA : rheumatoid arthritis</value></json:item></subject><arkIstex>ark:/67375/6H6-5QDQKMJM-F</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>Full-length article</json:string></originalGenre><abstract>Abstract: Copolymer 1 (Cop 1, poly [Y, E, A, K]) is a random synthetic amino acid copolymer effective in the treatment of relapsing forms of multiple sclerosis (MS), a disease that is linked to HLA-DR2 (DRB1∗1501). In the present study various peptides, synthesized according to the binding motifs for both the immunodominant epitope of myelin basic protein (MBP) 85-99, a candidate autoantigen in MS, and Cop 1, differentially inhibited binding of these antigens to disease-associated HLA-DR2 (DRB1∗1501) molecules. In particular, two peptides with residue K at position P-1, as referred to MBP 85-99, inhibited effectively the binding of both biotinylated MBP 85-99 and Cop 1 to HLA-DR2 molecules as well as IL-2 production by two MBP-specific HLA-DR2-restricted T-cell clones. These findings suggest the possible utility of these compounds or their more stable derivatives in treatment of MS.</abstract><qualityIndicators><score>8.644</score><pdfWordCount>5591</pdfWordCount><pdfCharCount>36096</pdfCharCount><pdfVersion>1.2</pdfVersion><pdfPageCount>11</pdfPageCount><pdfPageSize>596 x 792 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractWordCount>137</abstractWordCount><abstractCharCount>895</abstractCharCount><keywordCount>11</keywordCount></qualityIndicators><title>Synthetic peptides that inhibit binding of the myelin basic protein 85-99 epitope to multiple sclerosis-associated HLA-DR2 molecules and MBP-specific T-cell responses</title><pmid><json:string>11476898</json:string></pmid><pii><json:string>S0198-8859(01)00279-8</json:string></pii><genre><json:string>research-article</json:string></genre><host><title>Human Immunology</title><language><json:string>unknown</json:string></language><publicationDate>2001</publicationDate><issn><json:string>0198-8859</json:string></issn><pii><json:string>S0198-8859(00)X0079-1</json:string></pii><volume>62</volume><issue>8</issue><pages><first>753</first><last>763</last></pages><genre><json:string>journal</json:string></genre></host><namedEntities><unitex><date><json:string>2001</json:string></date><geogName></geogName><orgName><json:string>Elsevier Science Inc</json:string><json:string>Aarhus University Hospital, Skejby Sygehus, Aarhus N, Denmark</json:string><json:string>Elsevier Science Inc.</json:string><json:string>Department of Molecular and Cellular Biology</json:string><json:string>Department of Clinical Immunology</json:string><json:string>Harvard University</json:string><json:string>American Society</json:string><json:string>Dynatech, Chantilly</json:string><json:string>Sigma Chemical Co.</json:string><json:string>CA</json:string><json:string>National Institutes of Health</json:string></orgName><orgName_funder><json:string>CA</json:string><json:string>National Institutes of Health</json:string></orgName_funder><orgName_provider></orgName_provider><persName><json:string>Kai W. Wucherpfennig</json:string><json:string>Structural</json:string><json:string>Ob</json:string><json:string>Jack L. Strominger</json:string><json:string>In</json:string><json:string>Lincoln Park</json:string><json:string>Human Immunology</json:string><json:string>Lars Fugger</json:string><json:string>Hy</json:string></persName><placeName><json:string>Australia</json:string><json:string>Richmond</json:string><json:string>USA</json:string><json:string>CA</json:string><json:string>Israel</json:string><json:string>MA</json:string><json:string>Cambridge</json:string></placeName><ref_url></ref_url><ref_bibl><json:string>[50]</json:string><json:string>[45]</json:string><json:string>[18]</json:string><json:string>[22]</json:string><json:string>[39]</json:string><json:string>[43]</json:string><json:string>[49]</json:string><json:string>Histocompatibility and Immunogenetics, 2001</json:string><json:string>[42]</json:string><json:string>[4, 5]</json:string><json:string>[48]</json:string><json:string>[52]</json:string><json:string>[51]</json:string><json:string>[46]</json:string><json:string>M. Fridkis-Hareli et al.</json:string></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/6H6-5QDQKMJM-F</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><json:string>4 - immunopathologie</json:string></inist></categories><publicationDate>2001</publicationDate><copyrightDate>2001</copyrightDate><doi><json:string>10.1016/S0198-8859(01)00279-8</json:string></doi><id>0575E1F655B214465309154DC12F7A6C8421EFC7</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-5QDQKMJM-F/fulltext.pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-5QDQKMJM-F/bundle.zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/ark:/67375/6H6-5QDQKMJM-F/fulltext.tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Synthetic peptides that inhibit binding of the myelin basic protein 85-99 epitope to multiple sclerosis-associated HLA-DR2 molecules and MBP-specific T-cell responses</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher scheme="https://scientific-publisher.data.istex.fr">ELSEVIER</publisher><availability><licence><p>©2001 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>2001</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">FIGURE 1: Inhibition of biotinylated Cop 1 (A) and MBP 85-99 (B) binding to HLA-DR2 molecules by unlabeled Multipin peptides. Recombinant HLA-DR2 molecules were incubated with 1.5 μM of biotinylated Cop 1 (8,150) or 0.13 μM of biotinylated MBP 85-99 alone, or in the presence of unlabeled competitors at a range of concentrations. The signals at 410 nm in the alkaline phosphatase assay (see methods and materials section) without competitor were 0.90–0.95 and the background was 0.12.</note><note type="content">FIGURE 2: Inhibition of HLA-DR2-restricted MBP 84-102-specific T-cell transfectants Hy1B (panels A and B) and 8073 (panels C and D) in the presence of selected peptides. Irradiated MGAR (A and B) or L466 (C and D) cells were coincubated in duplicate with MBP 85-99 (final peptide concentration 12.5 μM) and different concentrations of the synthetic peptides or Cop 1 for 2 h at 37 °C, then T cells (Hy1B [A and B] or 8073 [C and D]) were added and incubated for 24 h at 37 °C. Supernatants (30 μl) were incubated with IL-2-dependent CTLL, followed by labeling with 3H-thymidine (1 μCi/well) for 12 h. Other details are as described in the materials and methods section.</note><note type="content">FIGURE 3: Detection of Cop 1-related peptides by anti-Cop 1 antibodies. Unlabeled Cop 1 or the synthetic peptides were diluted and plated in duplicates on a 96-well microtiter plates, followed by blocking with TBS/3% BSA and addition of biotinylated anti-Cop 1 polyclonal antibodies. For other details see the materials and methods section. Background levels were < 10% of the binding.</note><note type="content">TABLE 1: Affinity of the binding of the synthetic peptides to HLA-DR2 molecules, and inhibition of HLA-DR2-restricted MBP 84-102 specific T-cell clones</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Synthetic peptides that inhibit binding of the myelin basic protein 85-99 epitope to multiple sclerosis-associated HLA-DR2 molecules and MBP-specific T-cell responses</title><author xml:id="author-0000"><persName><forename type="first">Masha</forename><surname>Fridkis-Hareli</surname></persName><affiliation>Department of Molecular and Cellular Biology (M.F.-H., J.N.H.S., J.L.S.), Harvard University, Cambridge, MA, USA</affiliation></author><author xml:id="author-0001"><persName><forename type="first">Joel N.H</forename><surname>Stern</surname></persName><affiliation>Department of Molecular and Cellular Biology (M.F.-H., J.N.H.S., J.L.S.), Harvard University, Cambridge, MA, USA</affiliation></author><author xml:id="author-0002"><persName><forename type="first">Lars</forename><surname>Fugger</surname></persName><affiliation>Department of Clinical Immunology (L. F.), Aarhus University Hospital, Skejby Sygehus, Aarhus N, Denmark</affiliation></author><author xml:id="author-0003"><persName><forename type="first">Jack L</forename><surname>Strominger</surname></persName><email>jlstrom@fas.harvard.edu</email><note type="biography">Address reprint requests to: Jack L. Strominger, Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138; Tel: (617) 495-2733; Fax: (617) 496-8351</note><affiliation>Address reprint requests to: Jack L. Strominger, Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138; Tel: (617) 495-2733; Fax: (617) 496-8351</affiliation><affiliation>Department of Molecular and Cellular Biology (M.F.-H., J.N.H.S., J.L.S.), Harvard University, Cambridge, MA, USA</affiliation></author><idno type="istex">0575E1F655B214465309154DC12F7A6C8421EFC7</idno><idno type="ark">ark:/67375/6H6-5QDQKMJM-F</idno><idno type="DOI">10.1016/S0198-8859(01)00279-8</idno><idno type="PII">S0198-8859(01)00279-8</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)X0079-1</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="2001"></date><biblScope unit="volume">62</biblScope><biblScope unit="issue">8</biblScope><biblScope unit="page" from="753">753</biblScope><biblScope unit="page" to="763">763</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2001</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Abstract: Copolymer 1 (Cop 1, poly [Y, E, A, K]) is a random synthetic amino acid copolymer effective in the treatment of relapsing forms of multiple sclerosis (MS), a disease that is linked to HLA-DR2 (DRB1∗1501). In the present study various peptides, synthesized according to the binding motifs for both the immunodominant epitope of myelin basic protein (MBP) 85-99, a candidate autoantigen in MS, and Cop 1, differentially inhibited binding of these antigens to disease-associated HLA-DR2 (DRB1∗1501) molecules. In particular, two peptides with residue K at position P-1, as referred to MBP 85-99, inhibited effectively the binding of both biotinylated MBP 85-99 and Cop 1 to HLA-DR2 molecules as well as IL-2 production by two MBP-specific HLA-DR2-restricted T-cell clones. These findings suggest the possible utility of these compounds or their more stable derivatives in treatment of MS.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>MS</term></item><item><term>MBP</term></item><item><term>HLA-DR</term></item><item><term>Cop 1</term></item><item><term>T cells</term></item><item><term>peptides</term></item></list></keywords></textClass><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Abbreviations</head><item><term>Cop 1</term><term>copolymer 1</term></item><item><term>HA</term><term>influenza virus hemagglutinin</term></item><item><term>MBP</term><term>myelin basic protein</term></item><item><term>MS</term><term>multiple sclerosis</term></item><item><term>RA</term><term>rheumatoid arthritis</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2001">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-5QDQKMJM-F/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>5774</aid><ce:pii>S0198-8859(01)00279-8</ce:pii><ce:doi>10.1016/S0198-8859(01)00279-8</ce:doi><ce:copyright type="society" year="2001">American Society for Histocompatibility and Immunogenetics</ce:copyright></item-info><head><ce:title>Synthetic peptides that inhibit binding of the myelin basic protein 85-99 epitope to multiple sclerosis-associated HLA-DR2 molecules and MBP-specific T-cell responses</ce:title><ce:author-group><ce:author><ce:given-name>Masha</ce:given-name><ce:surname>Fridkis-Hareli</ce:surname><ce:cross-ref refid="AFF1"><ce:sup>a</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Joel N.H</ce:given-name><ce:surname>Stern</ce:surname><ce:cross-ref refid="AFF1"><ce:sup>a</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Lars</ce:given-name><ce:surname>Fugger</ce:surname><ce:cross-ref refid="AFF2"><ce:sup>b</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Jack L</ce:given-name><ce:surname>Strominger</ce:surname><ce:cross-ref refid="AFF1"><ce:sup>a</ce:sup></ce:cross-ref><ce:cross-ref refid="CORR1">*</ce:cross-ref><ce:e-address>jlstrom@fas.harvard.edu</ce:e-address></ce:author><ce:affiliation id="AFF1"><ce:label>a</ce:label><ce:textfn>Department of Molecular and Cellular Biology (M.F.-H., J.N.H.S., J.L.S.), Harvard University, Cambridge, MA, USA</ce:textfn></ce:affiliation><ce:affiliation id="AFF2"><ce:label>b</ce:label><ce:textfn>Department of Clinical Immunology (L. F.), Aarhus University Hospital, Skejby Sygehus, Aarhus N, Denmark</ce:textfn></ce:affiliation><ce:correspondence id="CORR1"><ce:label>*</ce:label><ce:text>Address reprint requests to: Jack L. Strominger, Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138; Tel: (617) 495-2733; Fax: (617) 496-8351</ce:text></ce:correspondence></ce:author-group><ce:date-received day="25" month="1" year="2001"></ce:date-received><ce:date-accepted day="22" month="5" year="2001"></ce:date-accepted><ce:abstract><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para>Copolymer 1 (Cop 1, poly [Y, E, A, K]) is a random synthetic amino acid copolymer effective in the treatment of relapsing forms of multiple sclerosis (MS), a disease that is linked to HLA-DR2 (DRB1∗1501). In the present study various peptides, synthesized according to the binding motifs for both the immunodominant epitope of myelin basic protein (MBP) 85-99, a candidate autoantigen in MS, and Cop 1, differentially inhibited binding of these antigens to disease-associated HLA-DR2 (DRB1∗1501) molecules. In particular, two peptides with residue K at position P-1, as referred to MBP 85-99, inhibited effectively the binding of both biotinylated MBP 85-99 and Cop 1 to HLA-DR2 molecules as well as IL-2 production by two MBP-specific HLA-DR2-restricted T-cell clones. These findings suggest the possible utility of these compounds or their more stable derivatives in treatment of MS.</ce:simple-para></ce:abstract-sec></ce:abstract><ce:keywords class="keyword"><ce:section-title>Keywords</ce:section-title><ce:keyword><ce:text>MS</ce:text></ce:keyword><ce:keyword><ce:text>MBP</ce:text></ce:keyword><ce:keyword><ce:text>HLA-DR</ce:text></ce:keyword><ce:keyword><ce:text>Cop 1</ce:text></ce:keyword><ce:keyword><ce:text>T cells</ce:text></ce:keyword><ce:keyword><ce:text>peptides</ce:text></ce:keyword></ce:keywords><ce:keywords class="abr"><ce:section-title>Abbreviations</ce:section-title><ce:keyword><ce:text>Cop 1</ce:text><ce:keyword><ce:text>copolymer 1</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>HA</ce:text><ce:keyword><ce:text>influenza virus hemagglutinin</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>MS</ce:text><ce:keyword><ce:text>multiple sclerosis</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>RA</ce:text><ce:keyword><ce:text>rheumatoid arthritis</ce:text></ce:keyword></ce:keyword></ce:keywords></head></converted-article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Synthetic peptides that inhibit binding of the myelin basic protein 85-99 epitope to multiple sclerosis-associated HLA-DR2 molecules and MBP-specific T-cell responses</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>Synthetic peptides that inhibit binding of the myelin basic protein 85-99 epitope to multiple sclerosis-associated HLA-DR2 molecules and MBP-specific T-cell responses</title></titleInfo><name type="personal"><namePart type="given">Masha</namePart><namePart type="family">Fridkis-Hareli</namePart><affiliation>Department of Molecular and Cellular Biology (M.F.-H., J.N.H.S., J.L.S.), Harvard University, Cambridge, MA, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Joel N.H</namePart><namePart type="family">Stern</namePart><affiliation>Department of Molecular and Cellular Biology (M.F.-H., J.N.H.S., J.L.S.), Harvard University, Cambridge, MA, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Lars</namePart><namePart type="family">Fugger</namePart><affiliation>Department of Clinical Immunology (L. F.), Aarhus University Hospital, Skejby Sygehus, Aarhus N, Denmark</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jack L</namePart><namePart type="family">Strominger</namePart><affiliation>E-mail: jlstrom@fas.harvard.edu</affiliation><affiliation>Department of Molecular and Cellular Biology (M.F.-H., J.N.H.S., J.L.S.), Harvard University, Cambridge, MA, USA</affiliation><description>Address reprint requests to: Jack L. Strominger, Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138; Tel: (617) 495-2733; Fax: (617) 496-8351</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">2001</dateIssued><copyrightDate encoding="w3cdtf">2001</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><abstract lang="en">Abstract: Copolymer 1 (Cop 1, poly [Y, E, A, K]) is a random synthetic amino acid copolymer effective in the treatment of relapsing forms of multiple sclerosis (MS), a disease that is linked to HLA-DR2 (DRB1∗1501). In the present study various peptides, synthesized according to the binding motifs for both the immunodominant epitope of myelin basic protein (MBP) 85-99, a candidate autoantigen in MS, and Cop 1, differentially inhibited binding of these antigens to disease-associated HLA-DR2 (DRB1∗1501) molecules. In particular, two peptides with residue K at position P-1, as referred to MBP 85-99, inhibited effectively the binding of both biotinylated MBP 85-99 and Cop 1 to HLA-DR2 molecules as well as IL-2 production by two MBP-specific HLA-DR2-restricted T-cell clones. These findings suggest the possible utility of these compounds or their more stable derivatives in treatment of MS.</abstract><note type="content">FIGURE 1: Inhibition of biotinylated Cop 1 (A) and MBP 85-99 (B) binding to HLA-DR2 molecules by unlabeled Multipin peptides. Recombinant HLA-DR2 molecules were incubated with 1.5 μM of biotinylated Cop 1 (8,150) or 0.13 μM of biotinylated MBP 85-99 alone, or in the presence of unlabeled competitors at a range of concentrations. The signals at 410 nm in the alkaline phosphatase assay (see methods and materials section) without competitor were 0.90–0.95 and the background was 0.12.</note><note type="content">FIGURE 2: Inhibition of HLA-DR2-restricted MBP 84-102-specific T-cell transfectants Hy1B (panels A and B) and 8073 (panels C and D) in the presence of selected peptides. Irradiated MGAR (A and B) or L466 (C and D) cells were coincubated in duplicate with MBP 85-99 (final peptide concentration 12.5 μM) and different concentrations of the synthetic peptides or Cop 1 for 2 h at 37 °C, then T cells (Hy1B [A and B] or 8073 [C and D]) were added and incubated for 24 h at 37 °C. Supernatants (30 μl) were incubated with IL-2-dependent CTLL, followed by labeling with 3H-thymidine (1 μCi/well) for 12 h. Other details are as described in the materials and methods section.</note><note type="content">FIGURE 3: Detection of Cop 1-related peptides by anti-Cop 1 antibodies. Unlabeled Cop 1 or the synthetic peptides were diluted and plated in duplicates on a 96-well microtiter plates, followed by blocking with TBS/3% BSA and addition of biotinylated anti-Cop 1 polyclonal antibodies. For other details see the materials and methods section. Background levels were < 10% of the binding.</note><note type="content">TABLE 1: Affinity of the binding of the synthetic peptides to HLA-DR2 molecules, and inhibition of HLA-DR2-restricted MBP 84-102 specific T-cell clones</note><subject lang="en"><genre>Keywords</genre><topic>MS</topic><topic>MBP</topic><topic>HLA-DR</topic><topic>Cop 1</topic><topic>T cells</topic><topic>peptides</topic></subject><subject lang="en"><genre>Abbreviations</genre><topic>Cop 1 : copolymer 1</topic><topic>HA : influenza virus hemagglutinin</topic><topic>MBP : myelin basic protein</topic><topic>MS : multiple sclerosis</topic><topic>RA : rheumatoid arthritis</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">2001</dateIssued></originInfo><identifier type="ISSN">0198-8859</identifier><identifier type="PII">S0198-8859(00)X0079-1</identifier><part><date>2001</date><detail type="volume"><number>62</number><caption>vol.</caption></detail><detail type="issue"><number>8</number><caption>no.</caption></detail><extent unit="issue-pages"><start>753</start><end>868</end></extent><extent unit="pages"><start>753</start><end>763</end></extent></part></relatedItem><identifier type="istex">0575E1F655B214465309154DC12F7A6C8421EFC7</identifier><identifier type="ark">ark:/67375/6H6-5QDQKMJM-F</identifier><identifier type="DOI">10.1016/S0198-8859(01)00279-8</identifier><identifier type="PII">S0198-8859(01)00279-8</identifier><accessCondition type="use and reproduction" contentType="copyright">©2001 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, ©2001</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-5QDQKMJM-F/record.json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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