人类白细胞抗原
班级(哲学)
抗体
生物
抗原
免疫学
计算生物学
计算机科学
人工智能
作者
Phillip Pymm,Philippa M. Saunders,Sushma Anand,Bruce J. MacLachlan,Camilla Faoro,Corinne Hitchen,Jamie Rossjohn,Andrëw G. Brööks,J.P. Vivian
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2024-08-02
卷期号:213 (6): 876-885
标识
DOI:10.4049/jimmunol.2400328
摘要
The central immunological role of HLA class I (HLA-I) in presenting peptide Ags to cellular components of the immune system has been the focus of intense study for >60 y. A confounding factor in the study of HLA-I has been the extreme polymorphism of these molecules. The mAb W6/32 has been a fundamental reagent bypassing the issue of polymorphism by recognizing an epitope that is conserved across diverse HLA-I allotypes. However, despite the widespread use of W6/32, the epitope of this Ab has not been definitively mapped. In this study, we present the crystal structure of the Fab fragment of W6/32 in complex with peptide-HLA-B*27:05. W6/32 bound to HLA-B*27:05 beneath the Ag-binding groove, recognizing a discontinuous epitope comprised of the α1, α2, and α3 domains of HLA-I and β2-microglobulin. The epitope comprises a region of low polymorphism reflecting the pan-HLA-I nature of the binding. Notably, the W6/32 epitope neither overlaps the HLA-I binding sites of either T cell Ag receptors or killer cell Ig-like receptors. However, it does coincide with the binding sites for leukocyte Ig-like receptors and CD8 coreceptors. Consistent with this, the use of W6/32 to block the interaction of NK cells with HLA-I only weakly impaired inhibition mediated by KIR3DL1, but impacted HLA-LILR recognition.
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