Highly avid, oligoclonal, early-differentiated antigen-specific CD8 ⁺ T cells in chronic HIV-2 infection

HIV-1-specific CD8⁺ T cells are present in most HIV-1-infected people and play an important role in controlling viral replication, but the characteristics of an effective HIV-specific T-cell response are largely unknown. The majority of HIV-2-infected people behave as long-term non-progressors while those who progress to AIDS do so in a manner indistinguishable from HIV-1. A detailed study of HIV-2 infection may identify protective immune responses. Robust gag p26-specific T-cell responses are elicited during HIV-2 infection and correlate with control of viremia. In this study, we analyzed features of an HLA-B*3501-restricted T-cell response to HIV-2 p26 that may contribute to virus control. In contrast to HIV-1, HIV-2-specific T cells are at an early stage of differentiation (CD27 ⁺ CD28⁺), a finding that relates directly to CD4 ⁺ T-cell levels and inversely to immune activation. The cells demonstrate IFN-γ secretion, oligoclonal T-cell receptor Vβ gene segment usage, exceptional avidity and secretion of pro-inflammatory cytokines. Despite the potentially strong selection pressure imposed on the virus by these cells, there was no evidence of HIV-2 sequence evolution. We propose that in chronic HIV-2 infection, the maintenance of early-differentiated, highly avid CD8⁺ T cells could account for the nonprogressive course of disease. Such responses may be desirable from an HIV vaccine.