HLA class I histocompatibility antigen, B alpha chain (HLA-B)

HLA class I histocompatibility antigen, B alpha chain (HLA-B) is a fundamental protein in the human immune system, serving as a cell surface receptor that presents endogenous peptides to CD8+ cytotoxic T cells [1, 2]. It plays a pivotal role in the adaptive immune response by allowing the immune system to distinguish between self and non-self, thereby facilitating the destruction of virally infected or cancerous cells [1]. HLA-B is characterized by extreme polymorphism, which contributes to its diverse roles in disease susceptibility, including strong associations with autoimmune disorders like ankylosing spondylitis (HLA-B*27) [2]. In the context of drug development and safety, HLA-B is a critical pharmacogenomic target because specific alleles can bind certain drugs or their metabolites, leading to severe, life-threatening immune-mediated adverse reactions [3]. For example, the HLA-B*57:01 allele is a mandatory biomarker for abacavir treatment to prevent hypersensitivity syndrome, and HLA-B*15:02 is a key predictor for carbamazepine-induced Stevens-Johnson syndrome [4]. Consequently, HLA-B is not only a target for understanding immune pathology but also a vital safety marker in clinical practice [3, 4].

Other names

MHC class I antigen BHLA-BMajor histocompatibility complex, class I, BASSPDA1Leukocyte antigen class I-B

HLA-B molecules function by binding and presenting endogenous peptides to the T-cell receptor (TCR) of CD8+ cytotoxic T cells [1]. In drug hypersensitivity, certain drugs bind non-covalently within the peptide-binding groove of specific HLA-B alleles (e.g., the F-pocket), altering the binding cleft's chemistry [3]. This change causes the HLA-B molecule to present a different repertoire of self-peptides, which are then recognized as foreign by T cells, triggering a systemic and often severe immune response [4].