Weak complex formation of adverse drug reaction-associated HLAB57, B58, and B15 molecules

In this study, we compared the molecular structures and intracellular localization of HLA-B*57:01, HLA-B*58:01, and HLA-B*15:02, which pose risks for developing drug hypersensitivity, as well as HLA-B*57:03 and HLA-B*15:01 that do not present such risks. We found that HLA molecules posing risks have a low affinity for the subunit β2-microglobulin; notably, the weak hydrogen bond formed via Gln96 of the HLA molecule contributes to this behavior. We also clarified that these HLA molecules are easily accumulated in the endoplasmic reticulum, exhibiting a low expression on the cell surface. Considering that these hypersensitivity risk-associated HLA molecules form complexes with β2-microglobulin and peptides in the endoplasmic reticulum, we assumed that their low complex formation ability in the endoplasmic reticulum facilitates the interaction with multiple drugs.PMID:35568130 | DOI:10.1016/j.tiv.2022.105383

Source: Toxicology in Vitro - May 14, 2022 Category: Toxicology Authors: Tomohiro Shirayanagi Akira Kazaoka Kenji Watanabe Liang Qu Naoki Sakamoto Tyuji Hoshino Kousei Ito Shigeki Aoki Source Type: research