Single cell, multiomic analysis of SIV specific CD8 T cells from multiple anatomical sites

CD8+ T cells contribute to the antiviral response in simian immunodeficiency virus (SIV) infection in nonhuman primates subsequent to recognition of viral epitopes via the T cell receptor (TCR). In previous studies, we examined the TCR repertoire of CD8+ T cells specific for a single SIV immunodominant epitope, Gag-CM9 (CTPYDINQM), throughout SIV infection. We identified tissue specific TCR sequences and TCRs shared by multiple anatomical sites. We now sought to evaluate if the tissue localization or TCR sequence of a CM9 specific CD8+ T cell corresponds with a transcriptional phenotype. CM9 specific CD8+ T cells were sorted from blood, lymph nodes, spleen, and liver from SIV infected rhesus macaques. The cells were processed through a single cell sequencing protocol, creating a TCR amplified library and an RNA gene expression library for each cell. Gene Set Enrichment Analysis (GSEA) revealed no distinct transcriptional profiles for CM9 specific CD8+ T cells between different anatomical sites and between cells with shared or tissue specific TCRs. Similarly, no clear transcriptional profiles were associated with public clonotypes. CM9 specific CD8+ T cells from posttreatment controllers did exhibit enrichment of select pathways compared to non-controllers. These data suggest that, while antigen specific CD8+ T cells from non-controllers exhibit largely similar transcriptional profiles, altered transcription in antigen specific CD8+ T cells from post-treatment controllers may associate with viral control. We sorted antigen specific CD8 T cells from blood and tissues from chronically infected rhesus macaques. We then completed scRNA and scTCR seq.