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

The Human Leukocyte Antigen class I (HLA-I) complex is a critical component of the adaptive immune system, consisting of a polymorphic alpha heavy chain and a non-covalently associated light chain, beta-2 microglobulin (B2M) (UniProt: P04439, P61769). Expressed on the surface of nearly all nucleated cells, these complexes present endogenous peptides to CD8+ cytotoxic T lymphocytes, allowing the immune system to detect and eliminate virally infected or malignant cells (NCBI: NBK27156). In oncology, the loss of HLA-I expression or mutations in B2M are common mechanisms by which tumors evade immune surveillance and develop resistance to checkpoint inhibitor therapies (PubMed: 28813417). HLA-I molecules are also the primary targets in transplant immunology, where mismatching between donor and recipient leads to organ rejection or graft-versus-host disease (PubMed: 25198550). Modern therapeutic strategies, such as TCR-T cell therapies and bispecific T-cell engagers like tebentafusp, specifically target peptide-HLA complexes to direct immune responses against cancer cells (DrugBank).

Other names

MHC class IMajor histocompatibility complex class IHLA-A/B/C complexClass I MHCHLA heavy chain and beta-2 microglobulin complex

HLA-I molecules present intracellularly derived peptides to the T-cell receptor (TCR) of CD8+ cytotoxic T lymphocytes, initiating an adaptive immune response (NCBI: NBK27156). They also serve as ligands for Killer-cell Immunoglobulin-like Receptors (KIRs) on Natural Killer (NK) cells, providing inhibitory signals that prevent the destruction of healthy self-cells (PubMed: 11244035).