HIV-1 envelope glycoprotein-derived peptides presented on MHC class I (HIV Env-MHC I)

HIV-1 envelope glycoprotein (Env) is a critical viral protein synthesized as a gp160 precursor and cleaved into gp120 and gp41 subunits, which mediate viral entry into host cells (UniProt P04578). During the viral life cycle, Env proteins are processed by the host cell's endogenous pathway into short peptides that are subsequently loaded onto Major Histocompatibility Complex (MHC) class I molecules for presentation on the cell surface (PubMed: 25692560). These peptide-MHC (pMHC) complexes serve as the primary targets for CD8+ cytotoxic T lymphocytes (CTLs), which recognize the viral fragments via their T-cell receptors (TCRs) (Nature: 10.1038/nature06746). In the context of therapeutic development, these complexes are targeted by engineered TCR-based therapies, such as ImmTAVs or TCR-T cells, to eliminate HIV-infected cells, including those in the latent reservoir (Immunocore). This approach is particularly valuable because it allows the immune system to identify infected cells even when whole viral particles are not being produced, provided that some level of viral protein synthesis occurs. However, the high mutational rate of HIV Env often leads to 'viral escape,' where mutations in the peptide sequence prevent MHC binding or TCR recognition, posing a significant challenge for sustained therapeutic efficacy (PubMed: 11752706).

Other names

HIV Env-HLA-I complexHIV-1 gp120/gp41-derived epitopes on MHC-IHIV Env pMHCEnvelope glycoprotein-derived peptide-MHC complex

Redirection of cytotoxic T-lymphocytes to recognize and lyse HIV-infected cells through high-affinity binding to the peptide-MHC complex.