Human immunodeficiency virus type 1 Gag polyprotein-derived peptide-major histocompatibility complex (HIV-1 Gag pMHC)

HIV-1 Gag antigens presented as peptide/MHC (pMHC) complexes are essential targets for the cellular immune system's ability to detect and eliminate HIV-infected cells. The Gag polyprotein (Pr55) is a major structural component of the virus that is processed into several smaller proteins, including p17 (matrix) and p24 (capsid). During infection, these proteins are degraded by the proteasome into short peptides, which are then transported into the endoplasmic reticulum and loaded onto Major Histocompatibility Complex (MHC) Class I molecules for surface display. These pMHC complexes are specifically recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes (CTLs). Because Gag is highly expressed and contains relatively conserved regions, it is a primary focus for immunotherapy, including TCR-engineered T-cell (TCR-T) therapies and therapeutic vaccines. These interventions aim to enhance the immune system's capacity to recognize and kill cells harboring the virus, including those in the latent reservoir, by mimicking or augmenting natural TCR-pMHC interactions.

Other names

HIV-1 Gag peptide-HLA complexGag p24 peptide-MHCGag p17 peptide-MHCHIV-1 Gag epitope-MHCPr55(Gag) peptide-MHC

Recognition of the Gag peptide-MHC complex by specific T-cell receptors (TCRs) triggers the activation of cytotoxic CD8+ T lymphocytes, leading to the targeted lysis of HIV-1 infected cells and the secretion of antiviral cytokines.