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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Escape from highly effective public CD8<sup>+</sup> T-cell clonotypes by HIV</title><author><name sortKey="Iglesias, Maria Candela" sort="Iglesias, Maria Candela" uniqKey="Iglesias M" first="Maria Candela" last="Iglesias">Maria Candela Iglesias</name><affiliation><nlm:aff id="aff1">Inserm UMR S 945, Infections and Immunity, Avenir Group, Université Pierre et Marie Curie-Paris 6, Hôpital Pitié-Salpêtrière, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Almeida, Jorge R" sort="Almeida, Jorge R" uniqKey="Almeida J" first="Jorge R." last="Almeida">Jorge R. Almeida</name><affiliation><nlm:aff id="aff1">Inserm UMR S 945, Infections and Immunity, Avenir Group, Université Pierre et Marie Curie-Paris 6, Hôpital Pitié-Salpêtrière, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;</nlm:aff></affiliation></author><author><name sortKey="Fastenackels, Solene" sort="Fastenackels, Solene" uniqKey="Fastenackels S" first="Solène" last="Fastenackels">Solène Fastenackels</name><affiliation><nlm:aff id="aff1">Inserm UMR S 945, Infections and Immunity, Avenir Group, Université Pierre et Marie Curie-Paris 6, Hôpital Pitié-Salpêtrière, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Van Bockel, David J" sort="Van Bockel, David J" uniqKey="Van Bockel D" first="David J." last="Van Bockel">David J. Van Bockel</name><affiliation><nlm:aff id="aff3">St Vincent's Centre for Applied Medical Research and the Kirby Institute, University of New South Wales, Darlinghurst, Australia;</nlm:aff></affiliation></author><author><name sortKey="Hashimoto, Masao" sort="Hashimoto, Masao" uniqKey="Hashimoto M" first="Masao" last="Hashimoto">Masao Hashimoto</name><affiliation><nlm:aff id="aff4">Division of Viral Immunology, Center for AIDS Research, Kumamoto University, Kumamoto, Japan;</nlm:aff></affiliation></author><author><name sortKey="Venturi, Vanessa" sort="Venturi, Vanessa" uniqKey="Venturi V" first="Vanessa" last="Venturi">Vanessa Venturi</name><affiliation><nlm:aff id="aff5">Computational Biology Group, Centre for Vascular Research, University of New South Wales, Kensington, Australia;</nlm:aff></affiliation></author><author><name sortKey="Gostick, Emma" sort="Gostick, Emma" uniqKey="Gostick E" first="Emma" last="Gostick">Emma Gostick</name><affiliation><nlm:aff id="aff6">Department of Infection, Immunity and Biochemistry, Cardiff University School of Medicine, Cardiff, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Urrutia, Alejandra" sort="Urrutia, Alejandra" uniqKey="Urrutia A" first="Alejandra" last="Urrutia">Alejandra Urrutia</name><affiliation><nlm:aff id="aff1">Inserm UMR S 945, Infections and Immunity, Avenir Group, Université Pierre et Marie Curie-Paris 6, Hôpital Pitié-Salpêtrière, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Wooldridge, Linda" sort="Wooldridge, Linda" uniqKey="Wooldridge L" first="Linda" last="Wooldridge">Linda Wooldridge</name><affiliation><nlm:aff id="aff6">Department of Infection, Immunity and Biochemistry, Cardiff University School of Medicine, Cardiff, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Clement, Mathew" sort="Clement, Mathew" uniqKey="Clement M" first="Mathew" last="Clement">Mathew Clement</name><affiliation><nlm:aff id="aff6">Department of Infection, Immunity and Biochemistry, Cardiff University School of Medicine, Cardiff, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Gras, Stephanie" sort="Gras, Stephanie" uniqKey="Gras S" first="Stéphanie" last="Gras">Stéphanie Gras</name><affiliation><nlm:aff id="aff7">Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Victoria, Australia;</nlm:aff></affiliation></author><author><name sortKey="Wilmann, Pascal G" sort="Wilmann, Pascal G" uniqKey="Wilmann P" first="Pascal G." last="Wilmann">Pascal G. Wilmann</name><affiliation><nlm:aff id="aff7">Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Victoria, Australia;</nlm:aff></affiliation></author><author><name sortKey="Autran, Brigitte" sort="Autran, Brigitte" uniqKey="Autran B" first="Brigitte" last="Autran">Brigitte Autran</name><affiliation><nlm:aff id="aff1">Inserm UMR S 945, Infections and Immunity, Avenir Group, Université Pierre et Marie Curie-Paris 6, Hôpital Pitié-Salpêtrière, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff8">AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Laboratoire d'Immunologie Cellulaire et Tissulaire, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Moris, Arnaud" sort="Moris, Arnaud" uniqKey="Moris A" first="Arnaud" last="Moris">Arnaud Moris</name><affiliation><nlm:aff id="aff1">Inserm UMR S 945, Infections and Immunity, Avenir Group, Université Pierre et Marie Curie-Paris 6, Hôpital Pitié-Salpêtrière, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Rossjohn, Jamie" sort="Rossjohn, Jamie" uniqKey="Rossjohn J" first="Jamie" last="Rossjohn">Jamie Rossjohn</name><affiliation><nlm:aff id="aff7">Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Victoria, Australia;</nlm:aff></affiliation></author><author><name sortKey="Davenport, Miles P" sort="Davenport, Miles P" uniqKey="Davenport M" first="Miles P." last="Davenport">Miles P. Davenport</name><affiliation><nlm:aff id="aff9">Complex Systems in Biology Group, Centre for Vascular Research, University of New South Wales, Kensington, Australia;</nlm:aff></affiliation></author><author><name sortKey="Takiguchi, Masafumi" sort="Takiguchi, Masafumi" uniqKey="Takiguchi M" first="Masafumi" last="Takiguchi">Masafumi Takiguchi</name><affiliation><nlm:aff id="aff4">Division of Viral Immunology, Center for AIDS Research, Kumamoto University, Kumamoto, Japan;</nlm:aff></affiliation></author><author><name sortKey="Brander, Christian" sort="Brander, Christian" uniqKey="Brander C" first="Christian" last="Brander">Christian Brander</name><affiliation><nlm:aff wicri:cut="; and" id="aff10">AIDS Research Institute IrsiCaixa–HIVACAT, Hospital Universitari Germans Trias i Pujol Ctra del Canyet, Barcelona, Spain</nlm:aff></affiliation><affiliation><nlm:aff id="aff11">Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain</nlm:aff></affiliation></author><author><name sortKey="Douek, Daniel C" sort="Douek, Daniel C" uniqKey="Douek D" first="Daniel C." last="Douek">Daniel C. Douek</name><affiliation><nlm:aff id="aff2">Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;</nlm:aff></affiliation></author><author><name sortKey="Kelleher, Anthony D" sort="Kelleher, Anthony D" uniqKey="Kelleher A" first="Anthony D." last="Kelleher">Anthony D. Kelleher</name><affiliation><nlm:aff id="aff3">St Vincent's Centre for Applied Medical Research and the Kirby Institute, University of New South Wales, Darlinghurst, Australia;</nlm:aff></affiliation></author><author><name sortKey="Price, David A" sort="Price, David A" uniqKey="Price D" first="David A." last="Price">David A. Price</name><affiliation><nlm:aff id="aff2">Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;</nlm:aff></affiliation><affiliation><nlm:aff id="aff6">Department of Infection, Immunity and Biochemistry, Cardiff University School of Medicine, Cardiff, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Appay, Victor" sort="Appay, Victor" uniqKey="Appay V" first="Victor" last="Appay">Victor Appay</name><affiliation><nlm:aff id="aff1">Inserm UMR S 945, Infections and Immunity, Avenir Group, Université Pierre et Marie Curie-Paris 6, Hôpital Pitié-Salpêtrière, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff8">AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Laboratoire d'Immunologie Cellulaire et Tissulaire, Paris, France;</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">21734237</idno><idno type="pmc">3162351</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3162351</idno><idno type="RBID">PMC:3162351</idno><idno type="doi">10.1182/blood-2011-01-328781</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">001791</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001791</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Escape from highly effective public CD8<sup>+</sup> T-cell clonotypes by HIV</title><author><name sortKey="Iglesias, Maria Candela" sort="Iglesias, Maria Candela" uniqKey="Iglesias M" first="Maria Candela" last="Iglesias">Maria Candela Iglesias</name><affiliation><nlm:aff id="aff1">Inserm UMR S 945, Infections and Immunity, Avenir Group, Université Pierre et Marie Curie-Paris 6, Hôpital Pitié-Salpêtrière, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Almeida, Jorge R" sort="Almeida, Jorge R" uniqKey="Almeida J" first="Jorge R." last="Almeida">Jorge R. Almeida</name><affiliation><nlm:aff id="aff1">Inserm UMR S 945, Infections and Immunity, Avenir Group, Université Pierre et Marie Curie-Paris 6, Hôpital Pitié-Salpêtrière, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;</nlm:aff></affiliation></author><author><name sortKey="Fastenackels, Solene" sort="Fastenackels, Solene" uniqKey="Fastenackels S" first="Solène" last="Fastenackels">Solène Fastenackels</name><affiliation><nlm:aff id="aff1">Inserm UMR S 945, Infections and Immunity, Avenir Group, Université Pierre et Marie Curie-Paris 6, Hôpital Pitié-Salpêtrière, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Van Bockel, David J" sort="Van Bockel, David J" uniqKey="Van Bockel D" first="David J." last="Van Bockel">David J. Van Bockel</name><affiliation><nlm:aff id="aff3">St Vincent's Centre for Applied Medical Research and the Kirby Institute, University of New South Wales, Darlinghurst, Australia;</nlm:aff></affiliation></author><author><name sortKey="Hashimoto, Masao" sort="Hashimoto, Masao" uniqKey="Hashimoto M" first="Masao" last="Hashimoto">Masao Hashimoto</name><affiliation><nlm:aff id="aff4">Division of Viral Immunology, Center for AIDS Research, Kumamoto University, Kumamoto, Japan;</nlm:aff></affiliation></author><author><name sortKey="Venturi, Vanessa" sort="Venturi, Vanessa" uniqKey="Venturi V" first="Vanessa" last="Venturi">Vanessa Venturi</name><affiliation><nlm:aff id="aff5">Computational Biology Group, Centre for Vascular Research, University of New South Wales, Kensington, Australia;</nlm:aff></affiliation></author><author><name sortKey="Gostick, Emma" sort="Gostick, Emma" uniqKey="Gostick E" first="Emma" last="Gostick">Emma Gostick</name><affiliation><nlm:aff id="aff6">Department of Infection, Immunity and Biochemistry, Cardiff University School of Medicine, Cardiff, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Urrutia, Alejandra" sort="Urrutia, Alejandra" uniqKey="Urrutia A" first="Alejandra" last="Urrutia">Alejandra Urrutia</name><affiliation><nlm:aff id="aff1">Inserm UMR S 945, Infections and Immunity, Avenir Group, Université Pierre et Marie Curie-Paris 6, Hôpital Pitié-Salpêtrière, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Wooldridge, Linda" sort="Wooldridge, Linda" uniqKey="Wooldridge L" first="Linda" last="Wooldridge">Linda Wooldridge</name><affiliation><nlm:aff id="aff6">Department of Infection, Immunity and Biochemistry, Cardiff University School of Medicine, Cardiff, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Clement, Mathew" sort="Clement, Mathew" uniqKey="Clement M" first="Mathew" last="Clement">Mathew Clement</name><affiliation><nlm:aff id="aff6">Department of Infection, Immunity and Biochemistry, Cardiff University School of Medicine, Cardiff, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Gras, Stephanie" sort="Gras, Stephanie" uniqKey="Gras S" first="Stéphanie" last="Gras">Stéphanie Gras</name><affiliation><nlm:aff id="aff7">Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Victoria, Australia;</nlm:aff></affiliation></author><author><name sortKey="Wilmann, Pascal G" sort="Wilmann, Pascal G" uniqKey="Wilmann P" first="Pascal G." last="Wilmann">Pascal G. Wilmann</name><affiliation><nlm:aff id="aff7">Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Victoria, Australia;</nlm:aff></affiliation></author><author><name sortKey="Autran, Brigitte" sort="Autran, Brigitte" uniqKey="Autran B" first="Brigitte" last="Autran">Brigitte Autran</name><affiliation><nlm:aff id="aff1">Inserm UMR S 945, Infections and Immunity, Avenir Group, Université Pierre et Marie Curie-Paris 6, Hôpital Pitié-Salpêtrière, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff8">AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Laboratoire d'Immunologie Cellulaire et Tissulaire, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Moris, Arnaud" sort="Moris, Arnaud" uniqKey="Moris A" first="Arnaud" last="Moris">Arnaud Moris</name><affiliation><nlm:aff id="aff1">Inserm UMR S 945, Infections and Immunity, Avenir Group, Université Pierre et Marie Curie-Paris 6, Hôpital Pitié-Salpêtrière, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Rossjohn, Jamie" sort="Rossjohn, Jamie" uniqKey="Rossjohn J" first="Jamie" last="Rossjohn">Jamie Rossjohn</name><affiliation><nlm:aff id="aff7">Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Victoria, Australia;</nlm:aff></affiliation></author><author><name sortKey="Davenport, Miles P" sort="Davenport, Miles P" uniqKey="Davenport M" first="Miles P." last="Davenport">Miles P. Davenport</name><affiliation><nlm:aff id="aff9">Complex Systems in Biology Group, Centre for Vascular Research, University of New South Wales, Kensington, Australia;</nlm:aff></affiliation></author><author><name sortKey="Takiguchi, Masafumi" sort="Takiguchi, Masafumi" uniqKey="Takiguchi M" first="Masafumi" last="Takiguchi">Masafumi Takiguchi</name><affiliation><nlm:aff id="aff4">Division of Viral Immunology, Center for AIDS Research, Kumamoto University, Kumamoto, Japan;</nlm:aff></affiliation></author><author><name sortKey="Brander, Christian" sort="Brander, Christian" uniqKey="Brander C" first="Christian" last="Brander">Christian Brander</name><affiliation><nlm:aff wicri:cut="; and" id="aff10">AIDS Research Institute IrsiCaixa–HIVACAT, Hospital Universitari Germans Trias i Pujol Ctra del Canyet, Barcelona, Spain</nlm:aff></affiliation><affiliation><nlm:aff id="aff11">Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain</nlm:aff></affiliation></author><author><name sortKey="Douek, Daniel C" sort="Douek, Daniel C" uniqKey="Douek D" first="Daniel C." last="Douek">Daniel C. Douek</name><affiliation><nlm:aff id="aff2">Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;</nlm:aff></affiliation></author><author><name sortKey="Kelleher, Anthony D" sort="Kelleher, Anthony D" uniqKey="Kelleher A" first="Anthony D." last="Kelleher">Anthony D. Kelleher</name><affiliation><nlm:aff id="aff3">St Vincent's Centre for Applied Medical Research and the Kirby Institute, University of New South Wales, Darlinghurst, Australia;</nlm:aff></affiliation></author><author><name sortKey="Price, David A" sort="Price, David A" uniqKey="Price D" first="David A." last="Price">David A. Price</name><affiliation><nlm:aff id="aff2">Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;</nlm:aff></affiliation><affiliation><nlm:aff id="aff6">Department of Infection, Immunity and Biochemistry, Cardiff University School of Medicine, Cardiff, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Appay, Victor" sort="Appay, Victor" uniqKey="Appay V" first="Victor" last="Appay">Victor Appay</name><affiliation><nlm:aff id="aff1">Inserm UMR S 945, Infections and Immunity, Avenir Group, Université Pierre et Marie Curie-Paris 6, Hôpital Pitié-Salpêtrière, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff8">AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Laboratoire d'Immunologie Cellulaire et Tissulaire, Paris, France;</nlm:aff></affiliation></author></analytic><series><title level="j">Blood</title><idno type="ISSN">0006-4971</idno><idno type="eISSN">1528-0020</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Mapping the precise determinants of T-cell efficacy against viruses in humans is a public health priority with crucial implications for vaccine design. To inform this effort, we performed a comprehensive analysis of the effective CD8<sup>+</sup> T-cell clonotypes that constitute responses specific for the HIV p24 Gag-derived KK10 epitope (KRWIILGLNK; residues 263-272) restricted by HLA-B*2705, which are known to confer superior control of viral replication in HIV-infected individuals. Particular KK10-specific CD8<sup>+</sup> T-cell clonotypes, characterized by <italic>TRBV4-3/TRBJ1-3</italic> gene rearrangements, were found to be preferentially selected in vivo and shared between individuals. These “public” clonotypes exhibit high levels of TCR avidity and Ag sensitivity, which impart functional advantages and enable effective suppression of HIV replication. The early L<sub>268</sub>M mutation at position 6 of the KK10 epitope enables the virus to avoid recognition by these highly effective CD8<sup>+</sup> T-cell clonotypes. However, alternative clonotypes with variant reactivity provide flexibility within the overall KK10-specific response. These findings provide refined mechanistic insights into the workings of an effective CD8<sup>+</sup> T-cell response against HIV.</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">Blood</journal-id><journal-id journal-id-type="hwp">bloodjournal</journal-id><journal-id journal-id-type="pmc">blood</journal-id><journal-id journal-id-type="publisher-id">Blood</journal-id><journal-title-group><journal-title>Blood</journal-title></journal-title-group><issn pub-type="ppub">0006-4971</issn><issn pub-type="epub">1528-0020</issn><publisher><publisher-name>American Society of Hematology</publisher-name><publisher-loc>Washington, DC</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">21734237</article-id><article-id pub-id-type="pmc">3162351</article-id><article-id pub-id-type="publisher-id">2011/328781</article-id><article-id pub-id-type="doi">10.1182/blood-2011-01-328781</article-id><article-categories><subj-group subj-group-type="heading"><subject>Immunobiology</subject></subj-group></article-categories><title-group><article-title>Escape from highly effective public CD8<sup>+</sup> T-cell clonotypes by HIV</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Iglesias</surname><given-names>Maria Candela</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="author-notes" rid="FN1">*</xref></contrib><contrib contrib-type="author"><name><surname>Almeida</surname><given-names>Jorge R.</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="author-notes" rid="FN1">*</xref></contrib><contrib contrib-type="author"><name><surname>Fastenackels</surname><given-names>Solène</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>van Bockel</surname><given-names>David J.</given-names></name><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Hashimoto</surname><given-names>Masao</given-names></name><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Venturi</surname><given-names>Vanessa</given-names></name><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Gostick</surname><given-names>Emma</given-names></name><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib contrib-type="author"><name><surname>Urrutia</surname><given-names>Alejandra</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Wooldridge</surname><given-names>Linda</given-names></name><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib contrib-type="author"><name><surname>Clement</surname><given-names>Mathew</given-names></name><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib contrib-type="author"><name><surname>Gras</surname><given-names>Stéphanie</given-names></name><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author"><name><surname>Wilmann</surname><given-names>Pascal G.</given-names></name><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author"><name><surname>Autran</surname><given-names>Brigitte</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff8">8</xref></contrib><contrib contrib-type="author"><name><surname>Moris</surname><given-names>Arnaud</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Rossjohn</surname><given-names>Jamie</given-names></name><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author"><name><surname>Davenport</surname><given-names>Miles P.</given-names></name><xref ref-type="aff" rid="aff9">9</xref></contrib><contrib contrib-type="author"><name><surname>Takiguchi</surname><given-names>Masafumi</given-names></name><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Brander</surname><given-names>Christian</given-names></name><xref ref-type="aff" rid="aff10">10</xref><xref ref-type="aff" rid="aff11">11</xref></contrib><contrib contrib-type="author"><name><surname>Douek</surname><given-names>Daniel C.</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Kelleher</surname><given-names>Anthony D.</given-names></name><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Price</surname><given-names>David A.</given-names></name><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Appay</surname><given-names>Victor</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff8">8</xref></contrib><aff id="aff1"><label>1</label>Inserm UMR S 945, Infections and Immunity, Avenir Group, Université Pierre et Marie Curie-Paris 6, Hôpital Pitié-Salpêtrière, Paris, France;</aff><aff id="aff2"><label>2</label>Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;</aff><aff id="aff3"><label>3</label>St Vincent's Centre for Applied Medical Research and the Kirby Institute, University of New South Wales, Darlinghurst, Australia;</aff><aff id="aff4"><label>4</label>Division of Viral Immunology, Center for AIDS Research, Kumamoto University, Kumamoto, Japan;</aff><aff id="aff5"><label>5</label>Computational Biology Group, Centre for Vascular Research, University of New South Wales, Kensington, Australia;</aff><aff id="aff6"><label>6</label>Department of Infection, Immunity and Biochemistry, Cardiff University School of Medicine, Cardiff, United Kingdom;</aff><aff id="aff7"><label>7</label>Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Victoria, Australia;</aff><aff id="aff8"><label>8</label>AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Laboratoire d'Immunologie Cellulaire et Tissulaire, Paris, France;</aff><aff id="aff9"><label>9</label>Complex Systems in Biology Group, Centre for Vascular Research, University of New South Wales, Kensington, Australia;</aff><aff id="aff10"><label>10</label>AIDS Research Institute IrsiCaixa–HIVACAT, Hospital Universitari Germans Trias i Pujol Ctra del Canyet, Barcelona, Spain; and</aff><aff id="aff11"><label>11</label>Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain</aff></contrib-group><author-notes><fn fn-type="equal" id="FN1"><label>*</label><p>M.C.I. and J.R.A. contributed equally to this work.</p></fn></author-notes><pub-date pub-type="ppub"><day>25</day><month>8</month><year>2011</year></pub-date><pub-date pub-type="epreprint"><day>6</day><month>7</month><year>2011</year></pub-date><pub-date pub-type="pmc-release"><day>25</day><month>8</month><year>2012</year></pub-date><pmc-comment> PMC Release delay is 12 months and 0 days and was based on the
<volume>118</volume><issue>8</issue><fpage>2138</fpage><lpage>2149</lpage><history><date date-type="received"><day>4</day><month>1</month><year>2011</year></date><date date-type="accepted"><day>20</day><month>6</month><year>2011</year></date></history><permissions><copyright-statement>© 2011 by The American Society of Hematology</copyright-statement><copyright-year>2011</copyright-year></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zh803411002138.pdf"></self-uri><abstract><p>Mapping the precise determinants of T-cell efficacy against viruses in humans is a public health priority with crucial implications for vaccine design. To inform this effort, we performed a comprehensive analysis of the effective CD8<sup>+</sup> T-cell clonotypes that constitute responses specific for the HIV p24 Gag-derived KK10 epitope (KRWIILGLNK; residues 263-272) restricted by HLA-B*2705, which are known to confer superior control of viral replication in HIV-infected individuals. Particular KK10-specific CD8<sup>+</sup> T-cell clonotypes, characterized by <italic>TRBV4-3/TRBJ1-3</italic> gene rearrangements, were found to be preferentially selected in vivo and shared between individuals. These “public” clonotypes exhibit high levels of TCR avidity and Ag sensitivity, which impart functional advantages and enable effective suppression of HIV replication. The early L<sub>268</sub>M mutation at position 6 of the KK10 epitope enables the virus to avoid recognition by these highly effective CD8<sup>+</sup> T-cell clonotypes. However, alternative clonotypes with variant reactivity provide flexibility within the overall KK10-specific response. These findings provide refined mechanistic insights into the workings of an effective CD8<sup>+</sup> T-cell response against HIV.</p></abstract><funding-group><award-group><funding-source id="CS100">National Institutes of Health</funding-source></award-group></funding-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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