Identification of a CD4 T-cell epitope in the hemagglutinin stalk domain of pandemic H1N1 influenza virus and its antigen-driven TCR usage signature in BALB/c mice
The stalk region of the influenza virus hemagglutinin is relatively well conserved compared with the globular head domain, which makes it a potential target for use as a universal vaccine against influenza. However, the role of CD4 T cells in the hemagglutinin stalk-specific immune response is not c...
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| Veröffentlicht in: | Cellular & molecular immunology 2017-06, Vol.14 (6), p.511-520 |
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| description | The stalk region of the influenza virus hemagglutinin is relatively well conserved compared with the globular head domain, which makes it a potential target for use as a universal vaccine against influenza. However, the role of CD4 T cells in the hemagglutinin stalk-specific immune response is not clear. Here we identified a mouse CD4 T-cell epitope that encompasses residues HA2
113-131
from the hemagglutinin stalk domain after a sub-lethal infection of influenza. In response to stimulation with the identified epitope, splenocytes derived from the infected mice showed significant polyfunctionality as shown by IL-2, TNF-α and IFN-γ production as well as degranulation. Moreover, mice immunized with the peptide corresponding to this CD4 T-cell epitope exhibited interindividual sharing of the CD4 T-cell receptor β sequences, and they had a higher survival rate following a challenge with a lethal dose of pandemic H1N1 influenza virus. Thus, our data demonstrated a crucial role of hemagglutinin stalk-specific CD4 T cells in the host immune response against influenza virus infection. |
| doi_str_mv | 10.1038/cmi.2016.20 |
| format | Article |
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113-131
from the hemagglutinin stalk domain after a sub-lethal infection of influenza. In response to stimulation with the identified epitope, splenocytes derived from the infected mice showed significant polyfunctionality as shown by IL-2, TNF-α and IFN-γ production as well as degranulation. Moreover, mice immunized with the peptide corresponding to this CD4 T-cell epitope exhibited interindividual sharing of the CD4 T-cell receptor β sequences, and they had a higher survival rate following a challenge with a lethal dose of pandemic H1N1 influenza virus. Thus, our data demonstrated a crucial role of hemagglutinin stalk-specific CD4 T cells in the host immune response against influenza virus infection.</description><identifier>ISSN: 1672-7681</identifier><identifier>EISSN: 2042-0226</identifier><identifier>DOI: 10.1038/cmi.2016.20</identifier><identifier>PMID: 27157498</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Animals ; Antibodies ; Biomedical and Life Sciences ; Biomedicine ; CD4 antigen ; CD4-Positive T-Lymphocytes - immunology ; Cytokines - metabolism ; Degranulation ; Epitope Mapping ; Epitopes ; Epitopes, T-Lymphocyte - immunology ; Epitopes, T-Lymphocyte - metabolism ; Female ; Hemagglutinin Glycoproteins, Influenza Virus - immunology ; Hemagglutinin Glycoproteins, Influenza Virus - metabolism ; Hemagglutinins ; Humans ; Immunology ; Influenza ; Influenza A Virus, H1N1 Subtype - physiology ; Influenza Vaccines - immunology ; Influenza, Human - immunology ; Interferon ; Interleukin 2 ; Lethal dose ; Lymphocyte Activation ; Lymphocytes T ; Medical Microbiology ; Mice ; Mice, Inbred BALB C ; Microbiology ; Orthomyxoviridae Infections - immunology ; Pandemics ; Receptors, Antigen, T-Cell - genetics ; research-article ; Rodents ; Splenocytes ; Swine flu ; T cell receptors ; Transcriptome ; Tumor necrosis factor ; Vaccine</subject><ispartof>Cellular & molecular immunology, 2017-06, Vol.14 (6), p.511-520</ispartof><rights>The Author(s) 2016</rights><rights>Copyright Nature Publishing Group Jun 2017</rights><rights>Copyright © 2016 Chinese Society of Immunology and The University of Science and Technology of China 2016 Chinese Society of Immunology and The University of Science and Technology of China</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c446t-7225f0eab9268011d25f3a5ce2a2802b20d2c9a77578db949b1b5aeea557a4743</citedby><cites>FETCH-LOGICAL-c446t-7225f0eab9268011d25f3a5ce2a2802b20d2c9a77578db949b1b5aeea557a4743</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5518815/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5518815/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27157498$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lu, I-Na</creatorcontrib><creatorcontrib>Farinelle, Sophie</creatorcontrib><creatorcontrib>Sausy, Aurélie</creatorcontrib><creatorcontrib>Muller, Claude P</creatorcontrib><title>Identification of a CD4 T-cell epitope in the hemagglutinin stalk domain of pandemic H1N1 influenza virus and its antigen-driven TCR usage signature in BALB/c mice</title><title>Cellular & molecular immunology</title><addtitle>Cell Mol Immunol</addtitle><addtitle>Cell Mol Immunol</addtitle><description>The stalk region of the influenza virus hemagglutinin is relatively well conserved compared with the globular head domain, which makes it a potential target for use as a universal vaccine against influenza. However, the role of CD4 T cells in the hemagglutinin stalk-specific immune response is not clear. Here we identified a mouse CD4 T-cell epitope that encompasses residues HA2
113-131
from the hemagglutinin stalk domain after a sub-lethal infection of influenza. In response to stimulation with the identified epitope, splenocytes derived from the infected mice showed significant polyfunctionality as shown by IL-2, TNF-α and IFN-γ production as well as degranulation. Moreover, mice immunized with the peptide corresponding to this CD4 T-cell epitope exhibited interindividual sharing of the CD4 T-cell receptor β sequences, and they had a higher survival rate following a challenge with a lethal dose of pandemic H1N1 influenza virus. Thus, our data demonstrated a crucial role of hemagglutinin stalk-specific CD4 T cells in the host immune response against influenza virus infection.</description><subject>Animals</subject><subject>Antibodies</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>CD4 antigen</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>Cytokines - metabolism</subject><subject>Degranulation</subject><subject>Epitope Mapping</subject><subject>Epitopes</subject><subject>Epitopes, T-Lymphocyte - immunology</subject><subject>Epitopes, T-Lymphocyte - metabolism</subject><subject>Female</subject><subject>Hemagglutinin Glycoproteins, Influenza Virus - immunology</subject><subject>Hemagglutinin Glycoproteins, Influenza Virus - metabolism</subject><subject>Hemagglutinins</subject><subject>Humans</subject><subject>Immunology</subject><subject>Influenza</subject><subject>Influenza A Virus, H1N1 Subtype - physiology</subject><subject>Influenza Vaccines - immunology</subject><subject>Influenza, Human - immunology</subject><subject>Interferon</subject><subject>Interleukin 2</subject><subject>Lethal dose</subject><subject>Lymphocyte Activation</subject><subject>Lymphocytes T</subject><subject>Medical Microbiology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Microbiology</subject><subject>Orthomyxoviridae Infections - immunology</subject><subject>Pandemics</subject><subject>Receptors, Antigen, T-Cell - genetics</subject><subject>research-article</subject><subject>Rodents</subject><subject>Splenocytes</subject><subject>Swine flu</subject><subject>T cell receptors</subject><subject>Transcriptome</subject><subject>Tumor necrosis factor</subject><subject>Vaccine</subject><issn>1672-7681</issn><issn>2042-0226</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNptkU1v1DAQhi0EokvhxB1Z4oIEaW1vHCcXpHb5aKUVSGg5W5NkknVJ7GA7K8Hf4Y_i3S1VQVw8sueZd8bzEvKcszPOluV5M5ozwXiRjgdkIVguMiZE8ZAseKFEpoqSn5AnIdwwJstc5Y_JiVBcqrwqF-TXdYs2ms40EI2z1HUU6OpdTjdZg8NAcTLRTUiNpXGLdIsj9P0wR2PTS4gwfKOtG8EcKiewLY6moVf8E08l3TCj_Ql0Z_wcaEpSE_cxmh5t1nqzQ0s3qy90DtAjDaa3EGd_6HZ5sb48b2hSw6fkUQdDwGe38ZR8_fB-s7rK1p8_Xq8u1lmT50XMlBCyYwh1JYqScd6m6xJkgwJEyUQtWCuaCpSSqmzrKq9qXktABCkVpL0sT8nbo-401yO2TVqMh0FP3ozgf2gHRv-dsWare7fTUvKy5DIJvLoV8O77jCHq0YT9GsGim4PmpSgKVUlRJPTlP-iNm71N39O8SmqqYIIl6vWRarwLwWN3Nwxnem--Tubrvfn6QL-4P_8d-8ftBLw5AiGlbI_-XtP_6P0GQ6q6FQ</recordid><startdate>20170601</startdate><enddate>20170601</enddate><creator>Lu, I-Na</creator><creator>Farinelle, Sophie</creator><creator>Sausy, Aurélie</creator><creator>Muller, Claude P</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170601</creationdate><title>Identification of a CD4 T-cell epitope in the hemagglutinin stalk domain of pandemic H1N1 influenza virus and its antigen-driven TCR usage signature in BALB/c mice</title><author>Lu, I-Na ; Farinelle, Sophie ; Sausy, Aurélie ; Muller, Claude P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c446t-7225f0eab9268011d25f3a5ce2a2802b20d2c9a77578db949b1b5aeea557a4743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Antibodies</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>CD4 antigen</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>Cytokines - metabolism</topic><topic>Degranulation</topic><topic>Epitope Mapping</topic><topic>Epitopes</topic><topic>Epitopes, T-Lymphocyte - immunology</topic><topic>Epitopes, T-Lymphocyte - metabolism</topic><topic>Female</topic><topic>Hemagglutinin Glycoproteins, Influenza Virus - immunology</topic><topic>Hemagglutinin Glycoproteins, Influenza Virus - metabolism</topic><topic>Hemagglutinins</topic><topic>Humans</topic><topic>Immunology</topic><topic>Influenza</topic><topic>Influenza A Virus, H1N1 Subtype - physiology</topic><topic>Influenza Vaccines - immunology</topic><topic>Influenza, Human - immunology</topic><topic>Interferon</topic><topic>Interleukin 2</topic><topic>Lethal dose</topic><topic>Lymphocyte Activation</topic><topic>Lymphocytes T</topic><topic>Medical Microbiology</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Microbiology</topic><topic>Orthomyxoviridae Infections - immunology</topic><topic>Pandemics</topic><topic>Receptors, Antigen, T-Cell - genetics</topic><topic>research-article</topic><topic>Rodents</topic><topic>Splenocytes</topic><topic>Swine flu</topic><topic>T cell receptors</topic><topic>Transcriptome</topic><topic>Tumor necrosis factor</topic><topic>Vaccine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lu, I-Na</creatorcontrib><creatorcontrib>Farinelle, Sophie</creatorcontrib><creatorcontrib>Sausy, Aurélie</creatorcontrib><creatorcontrib>Muller, Claude P</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cellular & molecular immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lu, I-Na</au><au>Farinelle, Sophie</au><au>Sausy, Aurélie</au><au>Muller, Claude P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of a CD4 T-cell epitope in the hemagglutinin stalk domain of pandemic H1N1 influenza virus and its antigen-driven TCR usage signature in BALB/c mice</atitle><jtitle>Cellular & molecular immunology</jtitle><stitle>Cell Mol Immunol</stitle><addtitle>Cell Mol Immunol</addtitle><date>2017-06-01</date><risdate>2017</risdate><volume>14</volume><issue>6</issue><spage>511</spage><epage>520</epage><pages>511-520</pages><issn>1672-7681</issn><eissn>2042-0226</eissn><abstract>The stalk region of the influenza virus hemagglutinin is relatively well conserved compared with the globular head domain, which makes it a potential target for use as a universal vaccine against influenza. However, the role of CD4 T cells in the hemagglutinin stalk-specific immune response is not clear. Here we identified a mouse CD4 T-cell epitope that encompasses residues HA2
113-131
from the hemagglutinin stalk domain after a sub-lethal infection of influenza. In response to stimulation with the identified epitope, splenocytes derived from the infected mice showed significant polyfunctionality as shown by IL-2, TNF-α and IFN-γ production as well as degranulation. Moreover, mice immunized with the peptide corresponding to this CD4 T-cell epitope exhibited interindividual sharing of the CD4 T-cell receptor β sequences, and they had a higher survival rate following a challenge with a lethal dose of pandemic H1N1 influenza virus. Thus, our data demonstrated a crucial role of hemagglutinin stalk-specific CD4 T cells in the host immune response against influenza virus infection.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>27157498</pmid><doi>10.1038/cmi.2016.20</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antibodies Biomedical and Life Sciences Biomedicine CD4 antigen CD4-Positive T-Lymphocytes - immunology Cytokines - metabolism Degranulation Epitope Mapping Epitopes Epitopes, T-Lymphocyte - immunology Epitopes, T-Lymphocyte - metabolism Female Hemagglutinin Glycoproteins, Influenza Virus - immunology Hemagglutinin Glycoproteins, Influenza Virus - metabolism Hemagglutinins Humans Immunology Influenza Influenza A Virus, H1N1 Subtype - physiology Influenza Vaccines - immunology Influenza, Human - immunology Interferon Interleukin 2 Lethal dose Lymphocyte Activation Lymphocytes T Medical Microbiology Mice Mice, Inbred BALB C Microbiology Orthomyxoviridae Infections - immunology Pandemics Receptors, Antigen, T-Cell - genetics research-article Rodents Splenocytes Swine flu T cell receptors Transcriptome Tumor necrosis factor Vaccine |
| title | Identification of a CD4 T-cell epitope in the hemagglutinin stalk domain of pandemic H1N1 influenza virus and its antigen-driven TCR usage signature in BALB/c mice |
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