Identification of novel HLA-E restricted HIV networked epitopes 4284

Abstract Description Numerous factors have made HIV vaccine development extremely difficult. Chief among them is Identifying epitopes capable of inducing CD8 T cell responses irrespective of variations in the human genetic makeup. We are therefore analyzing HIV-specific CD8 T cells restricted by HLA- E and targeting networked epitopes. The non-canonical HLA-E is of particular importance in that there are mainly 2 polymorphisms in the global population. Furthermore, it was previously demonstrated that CD8 T cell SIV epitopes restricted by major histocompatibility complex E (MHC-E), a homolog of HLA-E, indicating were essential for protection against the establishment of infection. To combat escape from CD8 T cells, epitopes shown to be structurally constrained were demonstrated to be targeted by individuals who naturally control HIV-1. We are examining structurally conserved CD8 T cell HIV epitopes restricted by HLA-E. Of the 11 structurally constrained epitopes, 8 were found to stabilize HLA-E on the cell surface. Antigen presenting cells that either expressed HLA-Ia or HLA-E alleles further demonstrated that 1 epitope induced polyfunctional HLA-E restricted CD8 T cell responses. Our results demonstrate that structurally constrained HLA-E restricted CD8 T cell epitopes can induce polyfunctional responses in PWH paving the way for a promising strategy for HIV vaccine design. Funding Sources Supported by R01 AI162168 Topic Categories Immune Mechanisms of Human Disease (HUM)