HIV-1 peptide–Major Histocompatibility Complex class I (HIV-1 pMHC-I)

HIV-1 peptide–Major Histocompatibility Complex class I (pMHC-I) complexes are the primary molecular signals used by the immune system to identify and eliminate HIV-infected cells. These complexes consist of short viral peptides, typically 8–11 amino acids in length, derived from viral proteins such as Gag, Pol, or Env, which are processed intracellularly and presented on the cell surface by MHC class I molecules (HLA). Recognition of these complexes by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes (CTLs) is essential for the natural immune control of HIV-1. However, the virus employs accessory proteins like Nef and Vpu to downregulate MHC-I expression, effectively hiding infected CD4+ T cells from immune detection. This downregulation, combined with rapid viral mutation leading to escape peptides, presents a significant challenge for the host immune response and the eradication of the latent reservoir. Therapeutic strategies targeting HIV-1 pMHC-I complexes aim to overcome these evasion tactics by using high-affinity synthetic receptors. These include soluble TCR-bispecific molecules, such as ImmTAVs (e.g., IMC-M113V), and TCR-mimic (TCRm) antibodies that can recognize rare or low-density viral antigens. These agents typically employ a bispecific format, with one arm binding the specific pMHC-I complex and the other arm engaging CD3 on polyclonal T cells to trigger targeted lysis of the infected cell. Such immunotherapies are currently being investigated as part of shock and kill strategies to eliminate the latent HIV reservoir and achieve a functional cure.

Other names

HIV-1 pMHC-I complexHIV-1 pHLA-IHIV-1 peptide-HLA class I complexHIV-1 antigen-MHC complexHIV-1 peptide-HLA-A*02:01 complex

T-cell redirection, TCR-mediated cytotoxicity, Targeted cell lysis