Human leukocyte antigen class I–peptide complex (HLA-I–peptide complex)

Human leukocyte antigen (HLA) class I–peptide complexes are essential molecules for the adaptive immune system's ability to monitor intracellular health. These complexes are composed of a polymorphic alpha heavy chain, a non-covalently associated beta-2 microglobulin (B2M) light chain, and a short peptide ligand, typically 8 to 11 amino acids in length (Source: NIH/NCBI). They are expressed on the surface of almost all nucleated cells, where they present fragments of endogenous proteins to CD8+ cytotoxic T lymphocytes. In the context of disease, these complexes present non-self peptides derived from viral proteins or tumor-specific mutations known as neoantigens, signaling the immune system to eliminate the compromised cell (Source: PubMed). Therapeutic strategies increasingly target specific HLA-peptide combinations using TCR-engineered T cells, bispecific T-cell engagers, and vaccines to achieve high specificity for malignant cells. However, challenges such as HLA downregulation by tumors and the risk of cross-reactivity with similar self peptides in healthy tissues remain significant hurdles in drug development (Source: Nature Reviews Drug Discovery).

Other names

MHC class I–peptide complexpHLAPeptide-MHC complexpMHC-IMajor histocompatibility complex class I–peptide complex

Recognition of specific peptide-HLA complexes by T-cell receptors (TCRs) or TCR-mimetic antibodies to induce T-cell mediated cytotoxicity against target cells.