HLA class I histocompatibility antigen, B alpha chain (HLA-B*35:01) (HLA-B*35:01)

HLA-B*35:01 is a specific allele of the Human Leukocyte Antigen B (HLA-B) gene, which encodes a Major Histocompatibility Complex (MHC) class I molecule (UniProt O19626). This protein plays a critical role in the adaptive immune system by presenting endogenous peptides to CD8+ cytotoxic T cells (RCSB 6BJ8). HLA-B*35:01 is particularly notable in pharmacogenomics due to its strong association with idiosyncratic drug-induced liver injury (DILI) and hypersensitivity reactions (Hepatology 2021, 73:2484-2493). It has been identified as a major risk factor for liver injury caused by nevirapine, trimethoprim-sulfamethoxazole, and certain herbal supplements like green tea extract and Polygonum multiflorum (Hepatology 2021, 73:1; J Ethnopharmacol 2024, 334:118523). Additionally, individuals carrying this allele often exhibit more rapid progression of HIV-1 infection to AIDS compared to those with other HLA-B alleles (AIDS 2011, 25:1185-1192). Understanding the structural interactions between drugs and the HLA-B*35:01 binding cleft is essential for predicting and preventing severe adverse drug reactions (ClinPGx).

Other names

MHC class I antigen HLA-B35HLA-B35B*3501Human leukocyte antigen B*35:01HLA-B*35:01:01:01

Drugs or their metabolites interact with the HLA-B*35:01 protein through mechanisms such as the hapten hypothesis (covalent binding to self-peptides), the p-i mechanism (non-covalent pharmacological interaction with immune receptors), or the altered peptide repertoire model (binding in the antigen-binding cleft to change presented peptides). These interactions trigger a CD8+ T-cell mediated immune response against host tissues.