HIV-1 Suppression by MHC class I restricted CD8 T Cells

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DESCRIPTION (provided by applicant): While animal model studies point to the importance of CD8 T cell responses in controlling HIV-1 replication, the specific quality of these cells achieving this control are unknown. Numerous studies have attempted to correlate different parameters of HIV-1 specific CD8 T cells with clinical markers of disease progression; however, inconsistent data has been attained. Also, for the studies that have seen correlations with plasma viral load, it is unclear whether the observed CD8 T cells parameter are just the result of low viral replication rather than a causative factor in controlling this replication. The problem stems from the fact that most assays do not measure the actual function of CD8 T cells in controlling HIV-1 but instead measure potential surrogate markers of this control. Specific Aim 1 of our proposal will analyze the efficiency of HIV-1 CD8 T cell clones in killing and suppressing HIV-1 replication using in vitro viral assays. Every clone will be identified on the basis T cell receptor ¿ gene (TCRB) sequencing. Using polychromatic flow cytometry in specific aim 2, we will sort HIV-1 specific CD8 T cells according to their capacity to express combinations of 4 different functional parameters (IFN-?, IL-2, TNF-a, and CD107). We will then determine which of the specific populations of HIV-1 CD8 T cells is enriched with clones that efficiently control virus in vitro. Our findings will have important implications fro HIV immunopathogenesis and vaccine design by supplying an HIV-1 specific CD8 T cell phenotype that results in efficient HIV-1 control.