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T-cell epitopes in Severe acute respiratory syndrome (SARS) coronavirus spike protein elicit a specific T-cell immune response in patients who recover from SARS

Identifieur interne : 005A56 ( Main/Exploration ); précédent : 005A55; suivant : 005A57

T-cell epitopes in Severe acute respiratory syndrome (SARS) coronavirus spike protein elicit a specific T-cell immune response in patients who recover from SARS

Auteurs : Yue-Dan Wang [République populaire de Chine, Hong Kong] ; Wan-Yee Fion Sin [Hong Kong] ; Guo-Bing Xu [République populaire de Chine] ; Huang-Hua Yang [Danemark] ; Tin-Yau Wong [Danemark] ; Xue-Wen Pang [République populaire de Chine] ; Xiao-Yan He [République populaire de Chine] ; Hua-Gang Zhang [République populaire de Chine] ; JOICE NA LEE NG [Danemark] ; Chak-Sum Samuel Cheng [Hong Kong] ; JING JU [Hong Kong] ; LI MENG [Hong Kong] ; Rui-Feng Yang [République populaire de Chine] ; Sik-To Lai [Danemark] ; Zhi-Hong Guo [Danemark] ; YONG XIE [Hong Kong] ; Wei-Feng Chen [République populaire de Chine]

Source :

RBID : Pascal:04-0314703

Descripteurs français

English descriptors

Abstract

The immunogenicity of HLA-A2-restricted T-cell epitopes in the S protein of the Severe acute respiratory syndrome coronavirus (SARS-CoV) and of human coronavirus strain 229e (HCoV-229e) was analyzed for the elicitation of a T-cell immune response in donors who had fully recovered from SARS-CoV infection. We employed online database analysis to compare the differences in the amino acid sequences of the homologous T epitopes of HCoV-229e and SARS-CoV. The identified T-cell epitope peptides were synthesized, and their binding affinities for HLA-A2 were validated and compared in the T2 cell system. The immunogenicity of all these peptides was assessed by using T cells obtained from donors who had fully recovered from SARS-CoV infection and from healthy donors with no history of SARS-CoV infection. HLA-A2 typing by indirect immunofluorescent antibody staining showed that 51.6% of SARS-CoV-infected patients were HLA-A2 positive. Online database analysis and the T2 cell binding test disclosed that the number of HLA-A2-restricted immunogenic epitopes of the S protein of SARS-CoV was decreased or even lost in comparison with the homologous sequences of the S protein of HCoV-229e. Among the peptides used in the study, the affinity of peptides from HCoV-229e (H77 and H881) and peptides from SARS-CoV (S978 and S1203) for binding to HLA-A2 was higher than that of other sequences. The gamma interferon (IFN-γ) release Elispot assay revealed that only SARS-CoV-specific peptides S1203 and S978 induced a high frequency of IFN-γ-secreting T-cell response in HLA-A2+ donors who had fully recovered from SARS-CoV infection; such a T-cell epitope-specific response was not observed in HLA-A2+ healthy donors or in HLA-A2- donors who had been infected with SARS-CoV after full recovery. Thus, T-cell epitopes S1203 and S978 are immunogenic and elicit an overt specific T-cell response in HLA-A2+ SARS-CoV-infected patients.

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Le document en format XML

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<s1>Department of Immunology, Peking University Health Science Centre</s1>
<s2>Beijing</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>17 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<placeName>
<settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Joice Na Lee Ng" sort="Joice Na Lee Ng" uniqKey="Joice Na Lee Ng" last="Joice Na Lee Ng">JOICE NA LEE NG</name>
<affiliation wicri:level="1">
<inist:fA14 i1="05">
<s1>Princess Margaret Hospital</s1>
<s3>DNK</s3>
<sZ>5 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>Danemark</country>
<wicri:noRegion>Princess Margaret Hospital</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Cheng, Chak Sum Samuel" sort="Cheng, Chak Sum Samuel" uniqKey="Cheng C" first="Chak-Sum Samuel" last="Cheng">Chak-Sum Samuel Cheng</name>
<affiliation wicri:level="1">
<inist:fA14 i1="02">
<s1>Department of Biology, Hong Kong University of Science and Technology, Clear Water Bay</s1>
<s2>Kowloon</s2>
<s3>HKG</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>Hong Kong</country>
<wicri:noRegion>Kowloon</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Jing Ju" sort="Jing Ju" uniqKey="Jing Ju" last="Jing Ju">JING JU</name>
<affiliation wicri:level="1">
<inist:fA14 i1="02">
<s1>Department of Biology, Hong Kong University of Science and Technology, Clear Water Bay</s1>
<s2>Kowloon</s2>
<s3>HKG</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>Hong Kong</country>
<wicri:noRegion>Kowloon</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Li Meng" sort="Li Meng" uniqKey="Li Meng" last="Li Meng">LI MENG</name>
<affiliation wicri:level="1">
<inist:fA14 i1="02">
<s1>Department of Biology, Hong Kong University of Science and Technology, Clear Water Bay</s1>
<s2>Kowloon</s2>
<s3>HKG</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>Hong Kong</country>
<wicri:noRegion>Kowloon</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Yang, Rui Feng" sort="Yang, Rui Feng" uniqKey="Yang R" first="Rui-Feng" last="Yang">Rui-Feng Yang</name>
<affiliation wicri:level="4">
<inist:fA14 i1="03">
<s1>First Hospital, Peking University</s1>
<s2>Beijing</s2>
<s3>CHN</s3>
<sZ>3 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<placeName>
<settlement type="city">Pékin</settlement>
</placeName>
<orgName type="university">Université de Pékin</orgName>
</affiliation>
</author>
<author>
<name sortKey="Lai, Sik To" sort="Lai, Sik To" uniqKey="Lai S" first="Sik-To" last="Lai">Sik-To Lai</name>
<affiliation wicri:level="1">
<inist:fA14 i1="05">
<s1>Princess Margaret Hospital</s1>
<s3>DNK</s3>
<sZ>5 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>Danemark</country>
<wicri:noRegion>Princess Margaret Hospital</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Guo, Zhi Hong" sort="Guo, Zhi Hong" uniqKey="Guo Z" first="Zhi-Hong" last="Guo">Zhi-Hong Guo</name>
<affiliation wicri:level="1">
<inist:fA14 i1="04">
<s1>Department of Chemistry, Hong Kong University of Science and Technology, Clear Water Bay</s1>
<s2>Kowloon</s2>
<s3>DNK</s3>
<sZ>4 aut.</sZ>
<sZ>15 aut.</sZ>
</inist:fA14>
<country>Danemark</country>
<wicri:noRegion>Kowloon</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Yong Xie" sort="Yong Xie" uniqKey="Yong Xie" last="Yong Xie">YONG XIE</name>
<affiliation wicri:level="1">
<inist:fA14 i1="02">
<s1>Department of Biology, Hong Kong University of Science and Technology, Clear Water Bay</s1>
<s2>Kowloon</s2>
<s3>HKG</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>Hong Kong</country>
<wicri:noRegion>Kowloon</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Chen, Wei Feng" sort="Chen, Wei Feng" uniqKey="Chen W" first="Wei-Feng" last="Chen">Wei-Feng Chen</name>
<affiliation wicri:level="3">
<inist:fA14 i1="01">
<s1>Department of Immunology, Peking University Health Science Centre</s1>
<s2>Beijing</s2>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>17 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<placeName>
<settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
</analytic>
<series>
<title level="j" type="main">Journal of virology</title>
<title level="j" type="abbreviated">J. virol.</title>
<idno type="ISSN">0022-538X</idno>
<imprint>
<date when="2004">2004</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt>
<title level="j" type="main">Journal of virology</title>
<title level="j" type="abbreviated">J. virol.</title>
<idno type="ISSN">0022-538X</idno>
</seriesStmt>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Amino Acid Sequence</term>
<term>Antigenic determinant</term>
<term>Cellular immunity</term>
<term>Coronavirus</term>
<term>Epitopes, T-Lymphocyte</term>
<term>HLA-A2 Antigen (analysis)</term>
<term>Human</term>
<term>Humans</term>
<term>Interferon-gamma (biosynthesis)</term>
<term>Membrane Glycoproteins (immunology)</term>
<term>Microbiology</term>
<term>Molecular Sequence Data</term>
<term>Protein A</term>
<term>SARS Virus (immunology)</term>
<term>Severe Acute Respiratory Syndrome (immunology)</term>
<term>Severe acute respiratory syndrome</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>T-Lymphocyte</term>
<term>T-Lymphocytes (immunology)</term>
<term>Viral Envelope Proteins (immunology)</term>
<term>Virology</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Antigène HLA-A2 (analyse)</term>
<term>Données de séquences moléculaires</term>
<term>Déterminants antigéniques des lymphocytes T</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines membranaires (immunologie)</term>
<term>Humains</term>
<term>Interféron gamma (biosynthèse)</term>
<term>Lymphocytes T (immunologie)</term>
<term>Protéines de l'enveloppe virale (immunologie)</term>
<term>Syndrome respiratoire aigu sévère (immunologie)</term>
<term>Séquence d'acides aminés</term>
<term>Virus du SRAS (immunologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en">
<term>HLA-A2 Antigen</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en">
<term>Interferon-gamma</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en">
<term>Membrane Glycoproteins</term>
<term>Viral Envelope Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" xml:lang="en">
<term>Epitopes, T-Lymphocyte</term>
<term>Spike Glycoprotein, Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="analyse" xml:lang="fr">
<term>Antigène HLA-A2</term>
</keywords>
<keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr">
<term>Interféron gamma</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr">
<term>Glycoprotéines membranaires</term>
<term>Lymphocytes T</term>
<term>Protéines de l'enveloppe virale</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en">
<term>SARS Virus</term>
<term>Severe Acute Respiratory Syndrome</term>
<term>T-Lymphocytes</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Amino Acid Sequence</term>
<term>Humans</term>
<term>Molecular Sequence Data</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr">
<term>Coronavirus</term>
<term>Données de séquences moléculaires</term>
<term>Déterminants antigéniques des lymphocytes T</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Homme</term>
<term>Humains</term>
<term>Lymphocyte T</term>
<term>Déterminant antigénique</term>
<term>Protéine A</term>
<term>Immunité cellulaire</term>
<term>Microbiologie</term>
<term>Séquence d'acides aminés</term>
<term>Virologie</term>
<term>Syndrome respiratoire aigu sévère</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr">
<term>Homme</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">The immunogenicity of HLA-A2-restricted T-cell epitopes in the S protein of the Severe acute respiratory syndrome coronavirus (SARS-CoV) and of human coronavirus strain 229e (HCoV-229e) was analyzed for the elicitation of a T-cell immune response in donors who had fully recovered from SARS-CoV infection. We employed online database analysis to compare the differences in the amino acid sequences of the homologous T epitopes of HCoV-229e and SARS-CoV. The identified T-cell epitope peptides were synthesized, and their binding affinities for HLA-A2 were validated and compared in the T2 cell system. The immunogenicity of all these peptides was assessed by using T cells obtained from donors who had fully recovered from SARS-CoV infection and from healthy donors with no history of SARS-CoV infection. HLA-A2 typing by indirect immunofluorescent antibody staining showed that 51.6% of SARS-CoV-infected patients were HLA-A2 positive. Online database analysis and the T2 cell binding test disclosed that the number of HLA-A2-restricted immunogenic epitopes of the S protein of SARS-CoV was decreased or even lost in comparison with the homologous sequences of the S protein of HCoV-229e. Among the peptides used in the study, the affinity of peptides from HCoV-229e (H77 and H881) and peptides from SARS-CoV (S978 and S1203) for binding to HLA-A2 was higher than that of other sequences. The gamma interferon (IFN-γ) release Elispot assay revealed that only SARS-CoV-specific peptides S1203 and S978 induced a high frequency of IFN-γ-secreting T-cell response in HLA-A2
<sup>+</sup>
donors who had fully recovered from SARS-CoV infection; such a T-cell epitope-specific response was not observed in HLA-A2
<sup>+</sup>
healthy donors or in HLA-A2- donors who had been infected with SARS-CoV after full recovery. Thus, T-cell epitopes S1203 and S978 are immunogenic and elicit an overt specific T-cell response in HLA-A2
<sup>+</sup>
SARS-CoV-infected patients.</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>Danemark</li>
<li>Hong Kong</li>
<li>République populaire de Chine</li>
</country>
<settlement>
<li>Pékin</li>
</settlement>
<orgName>
<li>Université de Pékin</li>
</orgName>
</list>
<tree>
<country name="République populaire de Chine">
<noRegion>
<name sortKey="Wang, Yue Dan" sort="Wang, Yue Dan" uniqKey="Wang Y" first="Yue-Dan" last="Wang">Yue-Dan Wang</name>
</noRegion>
<name sortKey="Chen, Wei Feng" sort="Chen, Wei Feng" uniqKey="Chen W" first="Wei-Feng" last="Chen">Wei-Feng Chen</name>
<name sortKey="He, Xiao Yan" sort="He, Xiao Yan" uniqKey="He X" first="Xiao-Yan" last="He">Xiao-Yan He</name>
<name sortKey="Pang, Xue Wen" sort="Pang, Xue Wen" uniqKey="Pang X" first="Xue-Wen" last="Pang">Xue-Wen Pang</name>
<name sortKey="Xu, Guo Bing" sort="Xu, Guo Bing" uniqKey="Xu G" first="Guo-Bing" last="Xu">Guo-Bing Xu</name>
<name sortKey="Yang, Rui Feng" sort="Yang, Rui Feng" uniqKey="Yang R" first="Rui-Feng" last="Yang">Rui-Feng Yang</name>
<name sortKey="Zhang, Hua Gang" sort="Zhang, Hua Gang" uniqKey="Zhang H" first="Hua-Gang" last="Zhang">Hua-Gang Zhang</name>
</country>
<country name="Hong Kong">
<noRegion>
<name sortKey="Wang, Yue Dan" sort="Wang, Yue Dan" uniqKey="Wang Y" first="Yue-Dan" last="Wang">Yue-Dan Wang</name>
</noRegion>
<name sortKey="Cheng, Chak Sum Samuel" sort="Cheng, Chak Sum Samuel" uniqKey="Cheng C" first="Chak-Sum Samuel" last="Cheng">Chak-Sum Samuel Cheng</name>
<name sortKey="Jing Ju" sort="Jing Ju" uniqKey="Jing Ju" last="Jing Ju">JING JU</name>
<name sortKey="Li Meng" sort="Li Meng" uniqKey="Li Meng" last="Li Meng">LI MENG</name>
<name sortKey="Sin, Wan Yee Fion" sort="Sin, Wan Yee Fion" uniqKey="Sin W" first="Wan-Yee Fion" last="Sin">Wan-Yee Fion Sin</name>
<name sortKey="Yong Xie" sort="Yong Xie" uniqKey="Yong Xie" last="Yong Xie">YONG XIE</name>
</country>
<country name="Danemark">
<noRegion>
<name sortKey="Yang, Huang Hua" sort="Yang, Huang Hua" uniqKey="Yang H" first="Huang-Hua" last="Yang">Huang-Hua Yang</name>
</noRegion>
<name sortKey="Guo, Zhi Hong" sort="Guo, Zhi Hong" uniqKey="Guo Z" first="Zhi-Hong" last="Guo">Zhi-Hong Guo</name>
<name sortKey="Joice Na Lee Ng" sort="Joice Na Lee Ng" uniqKey="Joice Na Lee Ng" last="Joice Na Lee Ng">JOICE NA LEE NG</name>
<name sortKey="Lai, Sik To" sort="Lai, Sik To" uniqKey="Lai S" first="Sik-To" last="Lai">Sik-To Lai</name>
<name sortKey="Wong, Tin Yau" sort="Wong, Tin Yau" uniqKey="Wong T" first="Tin-Yau" last="Wong">Tin-Yau Wong</name>
</country>
</tree>
</affiliations>
</record>

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