Examining the sequence and function of HIV Gag- specific T cell receptors restricted by HLA-B*57 and HLA-E

Antiretroviral therapy suppresses HIV viremia, but no vaccine or cure exists. Rare individuals who spontaneously control infection mount robust antiviral CD8 T cell responses, indicating that these cells are crucial. T cell receptors (TCR) recognize viral peptides presented on infected cells by HLA. HLA are diverse, but only classical HLA-A,-B, and -C alleles were thought to contribute to the HIV response. Recent studies identified T cells that recognize HIV Gag KF11 (KAFSPEVIPMF) presented by non- classical HLA-E, providing a new mechanism for control. My thesis examined the sequence and function of KF11-specific TCR in the context of HLA-B*57 and HLA-E. I identified seven highly functional TCR, including one likely dual HLA-restricted clone. These TCR displayed substantial sequence similarity and all required KF11 position 6 (E) for recognition. My results highlight features of KF11-specific TCR that may support efforts to develop a more effective vaccine to prevent HIV infection.