HIV-1 Gag-derived peptide-MHC class I complex (HIV Gag-pMHC I)

The HIV-1 Gag-derived peptide-MHC class I complex is a primary target for the cellular immune system's efforts to control HIV infection. The Gag polyprotein is a highly conserved structural component of the virus, and its degradation products are processed and presented on the surface of infected cells by Major Histocompatibility Complex (MHC) class I molecules. These complexes are specifically recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, which then initiate the destruction of the infected cell. Because Gag is relatively conserved compared to the viral envelope, it is a preferred target for next-generation immunotherapies, including TCR-engineered T cells (TCR-T) and bispecific molecules like ImmTAVs. However, the effectiveness of targeting these complexes is often challenged by 'viral escape,' where the virus evolves mutations that prevent peptide binding to MHC or recognition by TCRs. Additionally, these therapies are HLA-restricted, meaning they are only effective in patients with specific genetic backgrounds, such as those carrying the HLA-A*02 allele.

Other names

HIV Gag peptide-HLA complexGag-pMHCHIV-1 Gag epitope-MHC I complexSL9-HLA-A*02:01 complexHIV-1 Group-specific antigen peptide-MHC class I

Therapeutic agents such as TCR-engineered T cells or bispecific T-cell engagers (ImmTAVs) bind specifically to the Gag peptide presented within the MHC class I groove, triggering the activation of cytotoxic T lymphocytes to lyse HIV-infected cells.