Human leukocyte antigen A*24:02 peptide-MHC complex (HLA-A*24:02 pMHC)

The Human leukocyte antigen A*24:02 (HLA-A*24:02) peptide-MHC complex is a specific variant of the Major Histocompatibility Complex (MHC) class I molecule, primarily responsible for presenting endogenous peptides to CD8+ cytotoxic T cells. It consists of a polymorphic alpha heavy chain and a beta-2 microglobulin light chain, forming a binding groove that accommodates peptides typically 8 to 11 amino acids in length (UniProt: P01892). This allele is particularly significant in clinical immunology due to its high frequency in East Asian and Oceanian populations, serving as a cornerstone for the development of allele-specific immunotherapies (PMID: 28630458). In oncology, the HLA-A*24:02 complex presents various tumor-associated antigens, such as WT1 and NY-ESO-1, making it a primary target for T-cell receptor (TCR) engineered T-cell therapies and peptide-based vaccines (PMID: 31435466). Therapeutic interventions aim to exploit the specificity of the TCR-pMHC interaction to induce targeted lysis of malignant cells. However, the efficacy of these treatments can be hindered by tumor-mediated HLA downregulation or off-target cross-reactivity with similar self-peptides (PMID: 30224707).

Other names

HLA-A*24:02MHC class I antigen A*24:02HLA-A24Human MHC class I HLA-A*2402HLA-A*24:02 pMHC

The complex acts as a ligand for T-cell receptors (TCRs); drugs targeting this complex typically involve engineered TCRs or vaccines that enhance TCR-pMHC binding to induce cytotoxic T-lymphocyte (CTL) responses against target cells.