{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:10:30Z","timestamp":1790845830092,"version":"4.1.0"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"41","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,10,9]]},"abstract":"<jats:p>We studied CD8 T cell responses against HIV-1, cytomegalovirus, Epstein\u2013Barr virus, and influenza in 128 subjects and demonstrate that polyfunctional CD8 T cell responses, also including IL-2 production and Ag-specific proliferation, are predominantly driven by virus epitopes restricted by HLA-B alleles. Interestingly, these protective CD8 T cells are equipped with low-avidity T cell receptors (TCRs) for the cognate virus epitope. Conversely, HLA-A-restricted epitopes are mostly associated with \u201conly effector\u201d IFN-\u03b3-secreting, with cytotoxicity, and with the lack of IL-2 production and Ag-specific proliferation. These CD8 T cells are equipped with high-avidity TCR and express higher levels of the T cell exhaustion marker PD-1. Thus, the functional profile of the CD8 T cell response is strongly influenced by the extent to which there is stimulation of polyfunctional (predominantly restricted by HLA-B) versus only effector (restricted by HLA-A) T cell responses. These results provide the rationale for the observed protective role of HLA-B in HIV-1-infection and new insights into the relationship between TCR avidity, PD-1 expression, and the functional profile of CD8 T cells.<\/jats:p>","DOI":"10.1073\/pnas.0707570104","type":"journal-article","created":{"date-parts":[[2007,10,2]],"date-time":"2007-10-02T20:25:49Z","timestamp":1191356749000},"page":"16233-16238","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":116,"title":["Skewed association of polyfunctional antigen-specific CD8 T cell populations with HLA-B genotype"],"prefix":"10.1073","volume":"104","author":[{"given":"Alexandre","family":"Harari","sequence":"first","affiliation":[{"name":"Laboratory of AIDS Immunopathogenesis, Division of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Cellerai","sequence":"additional","affiliation":[{"name":"Laboratory of AIDS Immunopathogenesis, Division of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicitas Bellutti","family":"Enders","sequence":"additional","affiliation":[{"name":"Laboratory of AIDS Immunopathogenesis, Division of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"K\u00f6stler","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie und Hygiene, Universit\u00e4t Regensburg, D-93053 Regensburg, Germany; 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