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However, the factors that may contribute to the selection and expansion of CD8+ T\u2010cells in chronic HIV\u20102 infection, especially at the clonal level remain unclear. To address this question, we undertook a detailed molecular characterization of the clonotypic architecture of an HLA\u2010B*3501 restricted Gag\u2010specific CD8+ T\u2010cell response in donors chronically infected with HIV\u20102 using a combination of flow cytometry, tetramer\u2010specific CD8+ TCR clonotyping, and in vitro assays. We show that the response to the NY9 epitope is hierarchical and narrow in terms of T\u2010cell receptor\u2010alpha (TCRA) and \u2010beta (TCRB) gene usage yet clonotypically diverse. Furthermore, clonotypic dominance in shared origin CTL clones was associated with a greater magnitude of cytokine production and antigen sensitivity at limiting antigen dilution as well as enhanced cross\u2010reactivity for known HIV\u20102 variants. Hence, our data suggest that effector mobilization and expansion in human chronic HIV\u20102 infection may be linked to the qualitative features of specific CD8+ T\u2010cell clonotypes, which could have implications for viral control and disease outcome.<\/jats:p>","DOI":"10.1002\/eji.202048931","type":"journal-article","created":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T05:17:00Z","timestamp":1628486220000},"page":"2485-2500","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clonotypic architecture of a Gag\u2010specific CD8+ T\u2010cell response in chronic human HIV\u20102 infection"],"prefix":"10.1002","volume":"51","author":[{"given":"Eirini","family":"Moysi","sequence":"first","affiliation":[{"name":"Tissue Analysis Core, Vaccine Research Centre, Bethesda, National Institute of Allergy and Infectious Diseases (NIAID) National Institutes of Health (NIH)  Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Darko","sequence":"additional","affiliation":[{"name":"Human Immunology Section, Vaccine Research Center, NIAID NIH  Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ester","family":"Gea\u2010Mallorqu\u00ed","sequence":"additional","affiliation":[{"name":"Viral Immunology Unit Nuffield Department of Medicine  Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Constantinos","family":"Petrovas","sequence":"additional","affiliation":[{"name":"Tissue Analysis Core, Vaccine Research Centre, Bethesda, National Institute of Allergy and Infectious Diseases (NIAID) National Institutes of Health (NIH)  Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge R.","family":"Almeida","sequence":"additional","affiliation":[{"name":"Human Immunology Section, Vaccine Research Center, NIAID NIH  Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Wolinsky","sequence":"additional","affiliation":[{"name":"Human Immunology Section, Vaccine Research Center, NIAID NIH  Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanchun","family":"Peng","sequence":"additional","affiliation":[{"name":"MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine University of Oxford  Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Assan","family":"Jaye","sequence":"additional","affiliation":[{"name":"MRC Laboratories  The Gambia West Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillaume","family":"Stewart\u2010Jones","sequence":"additional","affiliation":[{"name":"Structural Biology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases National Institutes of Health  Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel C.","family":"Douek","sequence":"additional","affiliation":[{"name":"Human Immunology Section, Vaccine Research Center, NIAID NIH  Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard A.","family":"Koup","sequence":"additional","affiliation":[{"name":"Immunology Laboratory, Vaccine Research Center National Institute of Allergy and Infectious Diseases (NIAID) National Institutes of Health (NIH)  Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Dong","sequence":"additional","affiliation":[{"name":"MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine University of Oxford  Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5788-6998","authenticated-orcid":false,"given":"Sarah","family":"Rowland\u2010Jones","sequence":"additional","affiliation":[{"name":"Viral Immunology Unit Nuffield Department of Medicine  Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,9,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00126334-199205000-00010"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(18)30254-6"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7915856"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-199411000-00015"},{"key":"e_1_2_9_6_1","first-page":"457","article-title":"Low peripheral blood viral HIV\u20102 RNA in individuals with high CD4 percentage differentiates HIV\u20102 from HIV\u20101 infection","volume":"1","author":"Berry N.","year":"1998","journal-title":"J. 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