基于免疫的药物反应,如“阿巴卡韦超敏反应综合征”(AHS)和“卡马西平”-诱导的“Steven Johnson综合征”(SJS),已被与特定的“人白细胞抗原”(HLA)等位基因联系起来。
刊登在Nature上的文章中,作者介绍了一个机制,这些小分子药物通过该机制影响抗原呈现,进而影响T-细胞反应。通过以非共价方式与HLA-B*57:01的“抗原结合缝”相结合,“阿巴卡韦”诱导这个点的形状和化学性质发生变化,因而改变内生肽对HLA的亲和性。
最终,这将导致表现为AHS的系统性反应。研究人员发现,“卡马西平”也能与异形HLA-B*15:02结合、诱导一个类似的反应,这说明该机制具有普遍性。(生物谷Bioon.com)
doi:10.1038/nature11147
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Immune self-reactivity triggered by drug-modified HLA-peptide repertoire
Patricia T. Illing, Julian P. Vivian, Nadine L. Dudek, Lyudmila Kostenko, Zhenjun Chen, Mandvi Bharadwaj, John J. Miles, Lars Kjer-Nielsen, Stephanie Gras, Nicholas A. Williamson, Scott R. Burrows, Anthony W. Purcell, Jamie Rossjohn & James McCluskey
Human leukocyte antigens (HLAs) are highly polymorphic proteins that initiate immunity by presenting pathogen-derived peptides to T cells1. HLA polymorphisms mostly map to the antigen-binding cleft, thereby diversifying the repertoire of self-derived and pathogen-derived peptide antigens selected by different HLA allotypes2. A growing number of immunologically based drug reactions, including abacavir…