Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover

CD8+ T 细胞对 HIV-1 复制的优越控制体现在其亲和力、多功能性和克隆周转率上

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作者:Jorge R Almeida, David A Price, Laura Papagno, Zaïna Aït Arkoub, Delphine Sauce, Ethan Bornstein, Tedi E Asher, Assia Samri, Aurélie Schnuriger, Ioannis Theodorou, Dominique Costagliola, Christine Rouzioux, Henri Agut, Anne-Geneviève Marcelin, Daniel Douek, Brigitte Autran, Victor Appay

Abstract

The key attributes of CD8+ T cell protective immunity in human immunodeficiency virus (HIV) infection remain unclear. We report that CD8+ T cell responses specific for Gag and, in particular, the immunodominant p24 epitope KK10 correlate with control of HIV-1 replication in human histocompatibility leukocyte antigen (HLA)-B27 patients. To understand further the nature of CD8+ T cell-mediated antiviral efficacy, we performed a comprehensive study of CD8+ T cells specific for the HLA-B27-restricted epitope KK10 in chronic HIV-1 infection based on the use of multiparametric flow cytometry together with molecular clonotypic analysis and viral sequencing. We show that B27-KK10-specific CD8+ T cells are characterized by polyfunctional capabilities, increased clonal turnover, and superior functional avidity. Such attributes are interlinked and constitute the basis for effective control of HIV-1 replication. These data on the features of effective CD8+ T cells in HIV infection may aid in the development of successful T cell vaccines.

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