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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Novel Immunodominant Peptide Presentation Strategy: a Featured HLA-A*2402-Restricted Cytotoxic T-Lymphocyte Epitope Stabilized by Intrachain Hydrogen Bonds from Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Protein<xref ref-type="fn" rid="fn2">▿</xref>
<xref ref-type="fn" rid="fn3">†</xref>
</title>
<author><name sortKey="Liu, Jun" sort="Liu, Jun" uniqKey="Liu J" first="Jun" last="Liu">Jun Liu</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wu, Peng" sort="Wu, Peng" uniqKey="Wu P" first="Peng" last="Wu">Peng Wu</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Gao, Feng" sort="Gao, Feng" uniqKey="Gao F" first="Feng" last="Gao">Feng Gao</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Qi, Jianxun" sort="Qi, Jianxun" uniqKey="Qi J" first="Jianxun" last="Qi">Jianxun Qi</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kawana Tachikawa, Ai" sort="Kawana Tachikawa, Ai" uniqKey="Kawana Tachikawa A" first="Ai" last="Kawana-Tachikawa">Ai Kawana-Tachikawa</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Xie, Jing" sort="Xie, Jing" uniqKey="Xie J" first="Jing" last="Xie">Jing Xie</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Vavricka, Christopher J" sort="Vavricka, Christopher J" uniqKey="Vavricka C" first="Christopher J." last="Vavricka">Christopher J. Vavricka</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Iwamoto, Aikichi" sort="Iwamoto, Aikichi" uniqKey="Iwamoto A" first="Aikichi" last="Iwamoto">Aikichi Iwamoto</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Li, Taisheng" sort="Li, Taisheng" uniqKey="Li T" first="Taisheng" last="Li">Taisheng Li</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
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<idno type="pmid">20844028</idno>
<idno type="pmc">2977860</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2977860</idno>
<idno type="RBID">PMC:2977860</idno>
<idno type="doi">10.1128/JVI.01464-10</idno>
<date when="2010">2010</date>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Novel Immunodominant Peptide Presentation Strategy: a Featured HLA-A*2402-Restricted Cytotoxic T-Lymphocyte Epitope Stabilized by Intrachain Hydrogen Bonds from Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Protein<xref ref-type="fn" rid="fn2">▿</xref>
<xref ref-type="fn" rid="fn3">†</xref>
</title>
<author><name sortKey="Liu, Jun" sort="Liu, Jun" uniqKey="Liu J" first="Jun" last="Liu">Jun Liu</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wu, Peng" sort="Wu, Peng" uniqKey="Wu P" first="Peng" last="Wu">Peng Wu</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Gao, Feng" sort="Gao, Feng" uniqKey="Gao F" first="Feng" last="Gao">Feng Gao</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Qi, Jianxun" sort="Qi, Jianxun" uniqKey="Qi J" first="Jianxun" last="Qi">Jianxun Qi</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kawana Tachikawa, Ai" sort="Kawana Tachikawa, Ai" uniqKey="Kawana Tachikawa A" first="Ai" last="Kawana-Tachikawa">Ai Kawana-Tachikawa</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Xie, Jing" sort="Xie, Jing" uniqKey="Xie J" first="Jing" last="Xie">Jing Xie</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Vavricka, Christopher J" sort="Vavricka, Christopher J" uniqKey="Vavricka C" first="Christopher J." last="Vavricka">Christopher J. Vavricka</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Iwamoto, Aikichi" sort="Iwamoto, Aikichi" uniqKey="Iwamoto A" first="Aikichi" last="Iwamoto">Aikichi Iwamoto</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Li, Taisheng" sort="Li, Taisheng" uniqKey="Li T" first="Taisheng" last="Li">Taisheng Li</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
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</analytic>
<series><title level="j">Journal of Virology</title>
<idno type="ISSN">0022-538X</idno>
<idno type="eISSN">1098-5514</idno>
<imprint><date when="2010">2010</date>
</imprint>
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<front><div type="abstract" xml:lang="en"><p>Antigenic peptides recognized by virus-specific cytotoxic T lymphocytes (CTLs) are presented by major histocompatibility complex (MHC; or human leukocyte antigen [HLA] in humans) molecules, and the peptide selection and presentation strategy of the host has been studied to guide our understanding of cellular immunity and vaccine development. Here, a severe acute respiratory syndrome coronavirus (SARS-CoV) nucleocapsid (N) protein-derived CTL epitope, N1 (QFKDNVILL), restricted by HLA-A*2402 was identified by a series of <italic>in vitro</italic>
studies, including a computer-assisted algorithm for prediction, stabilization of the peptide by co-refolding with HLA-A*2402 heavy chain and β<sub>2</sub>
-microglobulin (β<sub>2</sub>
m), and T2-A24 cell binding. Consequently, the antigenicity of the peptide was confirmed by enzyme-linked immunospot (ELISPOT), proliferation assays, and HLA-peptide complex tetramer staining using peripheral blood mononuclear cells (PBMCs) from donors who had recovered from SARS donors. Furthermore, the crystal structure of HLA-A*2402 complexed with peptide N1 was determined, and the featured peptide was characterized with two unexpected intrachain hydrogen bonds which augment the central residues to bulge out of the binding groove. This may contribute to the T-cell receptor (TCR) interaction, showing a host immunodominant peptide presentation strategy. Meanwhile, a rapid and efficient strategy is presented for the determination of naturally presented CTL epitopes in the context of given HLA alleles of interest from long immunogenic overlapping peptides.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Virol</journal-id>
<journal-id journal-id-type="publisher-id">jvirol</journal-id>
<journal-title-group><journal-title>Journal of Virology</journal-title>
</journal-title-group>
<issn pub-type="ppub">0022-538X</issn>
<issn pub-type="epub">1098-5514</issn>
<publisher><publisher-name>American Society for Microbiology (ASM)</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">20844028</article-id>
<article-id pub-id-type="pmc">2977860</article-id>
<article-id pub-id-type="publisher-id">1464-10</article-id>
<article-id pub-id-type="doi">10.1128/JVI.01464-10</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Pathogenesis and Immunity</subject>
</subj-group>
</article-categories>
<title-group><article-title>Novel Immunodominant Peptide Presentation Strategy: a Featured HLA-A*2402-Restricted Cytotoxic T-Lymphocyte Epitope Stabilized by Intrachain Hydrogen Bonds from Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Protein<xref ref-type="fn" rid="fn2">▿</xref>
<xref ref-type="fn" rid="fn3">†</xref>
</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Liu</surname>
<given-names>Jun</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="aff" rid="aff1">2</xref>
<xref ref-type="aff" rid="aff1">3</xref>
<xref ref-type="fn" rid="fn1">‡</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wu</surname>
<given-names>Peng</given-names>
</name>
<xref ref-type="aff" rid="aff1">4</xref>
<xref ref-type="fn" rid="fn1">‡</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gao</surname>
<given-names>Feng</given-names>
</name>
<xref ref-type="aff" rid="aff1">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Qi</surname>
<given-names>Jianxun</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="aff" rid="aff1">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kawana-Tachikawa</surname>
<given-names>Ai</given-names>
</name>
<xref ref-type="aff" rid="aff1">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Xie</surname>
<given-names>Jing</given-names>
</name>
<xref ref-type="aff" rid="aff1">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Vavricka</surname>
<given-names>Christopher J.</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Iwamoto</surname>
<given-names>Aikichi</given-names>
</name>
<xref ref-type="aff" rid="aff1">6</xref>
<xref ref-type="aff" rid="aff1">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Li</surname>
<given-names>Taisheng</given-names>
</name>
<xref ref-type="aff" rid="aff1">4</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gao</surname>
<given-names>George F.</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="aff" rid="aff1">2</xref>
<xref ref-type="aff" rid="aff1">3</xref>
<xref ref-type="aff" rid="aff1">8</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
</contrib-group>
<aff id="aff1">CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, People's Republic of China,<label>1</label>
China-Japan Joint Laboratory of Molecular Immunology and Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China,<label>2</label>
College of Life Sciences, Graduate University, Chinese Academy of Sciences, Beijing 100049, People's Republic of China,<label>3</label>
Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, People's Republic of China,<label>4</label>
Institute of Biophysics (IBP), Chinese Academy of Sciences, Beijing 100101, China,<label>5</label>
Division of Infectious Diseases, Advanced Clinical Research Center, Department of Infectious Diseases and Applied Immunology, Research Hospital, University of Tokyo, Minato-ku, 108-8639 Tokyo, Japan,<label>6</label>
Institute of Medical Science, University of Tokyo, Minato-ku, 108-8639 Tokyo, Japan,<label>7</label>
Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, People's Republic of China<label>8</label>
</aff>
<author-notes><corresp id="cor1"><label>*</label>
Corresponding author. Mailing address for G. F. Gao: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, No. 1 Beichen West Road, Chaoyang District, Beijing 100101, People's Republic of China. Phone: (86)10-64807688. Fax: (86) 10-64807882. E-mail: <email>gaof@im.ac.cn</email>
. Mailing address for Taisheng Li: Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, People's Republic of China. Phone and fax: (86) 10-65295086. E-mail: <email>litsh@263.net</email>
</corresp>
<fn id="fn1"><label>‡</label>
<p>J. Liu and P. Wu contributed equally to this work.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><month>11</month>
<year>2010</year>
</pub-date>
<pub-date pub-type="epub"><day>15</day>
<month>9</month>
<year>2010</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>15</day>
<month>9</month>
<year>2010</year>
</pub-date>
<pmc-comment> PMC Release delay is 0 months and 0 days and was based on
/art/fm/atl/fn/p. </pmc-comment>
<volume>84</volume>
<issue>22</issue>
<fpage>11849</fpage>
<lpage>11857</lpage>
<history><date date-type="received"><day>13</day>
<month>7</month>
<year>2010</year>
</date>
<date date-type="accepted"><day>3</day>
<month>9</month>
<year>2010</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2010, American Society for Microbiology</copyright-statement>
<copyright-year>2010</copyright-year>
</permissions>
<self-uri xlink:title="pdf" xlink:href="zjv02210011849.pdf"></self-uri>
<abstract><p>Antigenic peptides recognized by virus-specific cytotoxic T lymphocytes (CTLs) are presented by major histocompatibility complex (MHC; or human leukocyte antigen [HLA] in humans) molecules, and the peptide selection and presentation strategy of the host has been studied to guide our understanding of cellular immunity and vaccine development. Here, a severe acute respiratory syndrome coronavirus (SARS-CoV) nucleocapsid (N) protein-derived CTL epitope, N1 (QFKDNVILL), restricted by HLA-A*2402 was identified by a series of <italic>in vitro</italic>
studies, including a computer-assisted algorithm for prediction, stabilization of the peptide by co-refolding with HLA-A*2402 heavy chain and β<sub>2</sub>
-microglobulin (β<sub>2</sub>
m), and T2-A24 cell binding. Consequently, the antigenicity of the peptide was confirmed by enzyme-linked immunospot (ELISPOT), proliferation assays, and HLA-peptide complex tetramer staining using peripheral blood mononuclear cells (PBMCs) from donors who had recovered from SARS donors. Furthermore, the crystal structure of HLA-A*2402 complexed with peptide N1 was determined, and the featured peptide was characterized with two unexpected intrachain hydrogen bonds which augment the central residues to bulge out of the binding groove. This may contribute to the T-cell receptor (TCR) interaction, showing a host immunodominant peptide presentation strategy. Meanwhile, a rapid and efficient strategy is presented for the determination of naturally presented CTL epitopes in the context of given HLA alleles of interest from long immunogenic overlapping peptides.</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>
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