HLA class I histocompatibility antigen, B-15 alpha chain (HLA-B*15:02) (HLA-B*15:02)

HLA-B*15:02 is a specific allele of the Human Leukocyte Antigen B gene, which encodes a major histocompatibility complex (MHC) class I molecule. This protein plays a critical role in the immune system by presenting endogenous peptides to CD8+ cytotoxic T-cells [1]. In certain populations, particularly those of East and Southeast Asian descent, the presence of this allele is strongly associated with a high risk of developing severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), when exposed to the anticonvulsant drug carbamazepine [2, 3]. The drug is thought to bind directly to the HLA-B*15:02 molecule, altering its peptide-binding specificity or directly stimulating T-cell receptors, leading to massive keratinocyte death [4]. Due to this strong association, the FDA and other regulatory bodies recommend genetic screening for HLA-B*15:02 before initiating carbamazepine therapy in at-risk populations [2]. Beyond carbamazepine, other aromatic anticonvulsants like phenytoin and oxcarbazepine have also been implicated in similar immune-mediated reactions in HLA-B*15:02 carriers [3]. The identification of this protein as a risk factor represents a landmark in pharmacogenomics, allowing for the prevention of life-threatening adverse drug events through personalized medicine.

Other names

HLA-B1502MHC class I antigen B*15:02Human leukocyte antigen B*15:02Major histocompatibility complex, class I, B

The drug (e.g., carbamazepine) binds non-covalently to the antigen-binding groove of the HLA-B*15:02 molecule, which triggers an inappropriate T-cell mediated immune response against keratinocytes [3, 4].