Human leukocyte antigen class I (HLA-A and HLA-B) (HLA-A/B)

Human leukocyte antigen (HLA) class I molecules, specifically those encoded by the classical HLA-A and HLA-B loci, are cell-surface glycoproteins that play a fundamental role in the adaptive immune system [4, 10, 15]. They function by presenting processed endogenous peptide fragments to CD8+ cytotoxic T lymphocytes via the T-cell receptor (TCR), allowing the immune system to identify and eliminate cells that are virally infected or malignantly transformed [1, 3, 5, 10]. HLA-A and HLA-B are highly polymorphic, with diverse alleles dictating an individual's unique immune profile and disease susceptibility [9, 15]. In oncology, specific HLA alleles serve as the target platform for TCR-engineered T-cell therapies and bispecific proteins like tebentafusp, which recognize specific peptide-HLA complexes on tumor cells [1]. Furthermore, these molecules are critical in transplant medicine, where donor-recipient mismatching triggers graft rejection or graft-versus-host disease [4, 13, 14]. Certain HLA alleles also mediate life-threatening drug hypersensitivity reactions, such as Stevens-Johnson Syndrome, by non-covalently binding specific drugs (e.g., abacavir or carbamazepine) and triggering off-target T-cell activation [6, 11, 15].

Other names

Major histocompatibility complex class IMHC class IHLA-AHLA-BHuman leukocyte antigen AHuman leukocyte antigen B

MHC-restricted peptide presentation to T-cell receptors (TCRs); TCR-mimetic binding for tumor targeting; pharmacologic interaction with immune receptors (p-i) concept; induction of an altered peptide repertoire