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

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.