HIV-1 Pol-derived peptides presented by MHC class I (HIV-1 Pol/MHC-I)

HIV-1 Pol-derived peptides presented by MHC class I molecules are essential targets for cellular immunity and immunotherapy against HIV-1 (Walker et al., Nature, 1987; PMID: 3474518). The Pol polyprotein encodes vital viral enzymes, including reverse transcriptase, protease, and integrase, which are highly conserved and necessary for the viral life cycle (Kundu et al., Frontiers in Immunology, 2020; PMID: 32117331). During infection, these proteins are proteolytically processed into short peptides that are loaded onto MHC class I molecules and displayed on the cell surface for recognition by CD8+ cytotoxic T lymphocytes (CTLs). Therapeutic interventions such as TCR-engineered T cells (TCR-T) and Immune Mobilizing Monoclonal TCRs Against Viruses (ImmTAVs) are being developed to specifically bind these Pol-derived pMHC complexes and eliminate infected cells (Vora et al., Journal of Virology, 2016; PMID: 27440892). By targeting conserved Pol epitopes, these therapies aim to provide a broad-spectrum immune response that is less susceptible to viral mutation. However, a significant challenge is the HIV-mediated downregulation of MHC class I by the Nef protein, which reduces target density on the cell surface (Collins et al., Nature, 1998; PMID: 9497286). Additionally, the potential for off-target cross-reactivity with human self-peptides requires rigorous safety evaluation during drug development.

Other names

HIV-1 Pol pMHCHIV-1 Pol epitope-HLA complexHIV-1 Polymerase-derived peptide-MHC class I complexHIV-1 Pol peptide-MHC complex

Engineered T-cell receptors (TCRs) or TCR-like molecules bind specifically to the HIV-1 Pol peptide-MHC complex on the surface of infected cells, triggering T-cell mediated cytotoxicity and the release of effector cytokines to eliminate the viral reservoir.