HIV-1 peptide-HLA class I complex (HIV-1 pHLA-I)

HIV-1–derived peptide–HLA class I complexes are molecular assemblies presented on the surface of cells infected with the Human Immunodeficiency Virus type 1 (HIV-1). These complexes are formed when viral proteins, such as Gag, Pol, or Env, are processed by the host cell's proteasome into short peptides, which are then loaded onto Human Leukocyte Antigen (HLA) class I molecules (HLA-A, -B, -C, or -E) in the endoplasmic reticulum (Frontiers in Immunology, 2023). The primary biological role of these complexes is to serve as ligands for the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes (CTLs), signaling the presence of an intracellular infection and triggering an immune response (PNAS, 1998). HIV-1 employs several evasion strategies, most notably the Nef-mediated downregulation of HLA-A and HLA-B molecules, to reduce the visibility of infected cells to the immune system (NIH, 2016). These complexes are critical for the natural control of HIV-1, as certain HLA alleles, such as HLA-B*57:01, are associated with elite control of the virus due to superior presentation of conserved epitopes. Therapeutic approaches targeting these complexes include TCR-engineered T cells and bispecific molecules like ImmTAVs (Immune mobilizing monoclonal TCRs against Virus), such as IMC-HIVV, which redirect T cells to recognize and kill infected cells even at low antigen densities (Wallace et al., 2024). Modern drug development focuses on using high-affinity, soluble TCRs to overcome viral evasion tactics and provide a potent stimulus for viral clearance, particularly in the context of eliminating the latent HIV reservoir.

Other names

HIV-1 peptide-MHC class I complexHIV-1 pMHC-IHIV-1 pHLA-IHIV-1 antigen-HLA complexHIV-1 epitope-HLA complex

T-cell redirection and induction of cytotoxic T-lymphocyte-mediated lysis of HIV-infected cells