Major histocompatibility complex molecules presenting HIV-1 Env peptides (HIV-1 Env pMHC)

Major histocompatibility complex (MHC) molecules presenting HIV-1 Envelope (Env) peptides are protein complexes found on the surface of HIV-infected cells that serve as the primary recognition signal for the adaptive immune system (Sengupta et al., 2022). These complexes consist of a Human Leukocyte Antigen (HLA) molecule, typically MHC Class I, bound to a short peptide fragment derived from the HIV-1 Env glycoproteins gp120 or gp41 (Board et al., 2022). Recognition of these peptide-MHC (pMHC) complexes by T-cell receptors (TCRs) on CD8+ T cells triggers the destruction of the infected cell, making them a critical target for immunotherapies aimed at curing HIV (Immunocore, 2023). Modern therapeutic strategies, such as TCR-mimic (TCRm) antibodies and ImmTAVs (Immune-mobilizing monoclonal TCRs Against Viruses), are designed to bind these pMHC complexes with high affinity to redirect T-cell cytotoxicity toward the viral reservoir (Sengupta et al., 2022). However, the effectiveness of targeting Env-derived pMHC is often limited by the extreme sequence variability of the Env protein and the virus's ability to downregulate MHC expression via the Nef protein (Stumptner-Cuvelette et al., 2001).

Other names

HIV-1 Env peptide-MHC complexHIV-1 Env pHLAHIV-1 Env pMHCHLA-restricted HIV-1 Env epitopesMHC-I presenting HIV-1 Env peptides

T-cell redirection and activation, leading to the formation of an immunological synapse and subsequent lysis of HIV-infected cells via the release of perforin and granzymes.