Deep sequencing of the gag-specific CD4+ T cell receptor repertoire and CD4+ memory subsets of HIV viral controllers reveals significant sharing of unique gag-specific TCRs in central and effector memory TCR repertoires (LYM3P.742)

Abstract

Abstract HIV viral controllers maintain preserved CD4+ T cells counts and undetectable viral levels off antiretroviral therapy. The diversity of the HIV-specific T cell receptor (TCR) repertoire within memory may be important for maintaining viral control, however, sequencing the entire CD4+ memory repertoire to evaluate for HIV specific TCRs would be prohibitive by conventional methods. In this study, the TCR repertoire of two HIV controllers was analyzed with deep sequencing. Peripheral blood mononuclear cells (PBMC) of HIV+ individuals were stimulated by Gag peptides and the Gag-specific CD4+ T cells were sorted by expression of the activation markers. Unstimulated PBMC were sorted for CD4+ memory subsets based on central memory (CD45RO+CCR7+), effector memory (CD45RO+CCR7-), and naïve (CD45RO-CCR7+). Subject 1 had 46 Gag-specific CD4+ TCR. 18 were in the Tcm population and 24 in the Tem population, though 15 of these sequences were identified in both subsets. In Subject 2, there were 29 Gag-specific TCR with 27 in the Tcm population and 20 in the Tem repertoire with 20 Gag-specific TCR identified in both populations. Deep sequencing of the HIV specific TCR repertoire and unbiased memory subsets revealed a high degree of overlap of CD4+ HIV-specific cells in both the Tcm and Tem populations. Further studies will need to be performed to determine if this provides an advantage for virologic control.