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MHC-II 动力学在 HLA-DR 同种异型中得以维持，以确保催化肽交换。

MHC-II dynamics are maintained in HLA-DR allotypes to ensure catalyzed peptide exchange.

机构信息

Protein Biochemistry, Institute for Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany.

Department of Mathematics and Computer Science, Freie Universität Berlin, Berlin, Germany.

出版信息

Nat Chem Biol. 2023 Oct;19(10):1196-1204. doi: 10.1038/s41589-023-01316-3. Epub 2023 May 4.

DOI:10.1038/s41589-023-01316-3
PMID:37142807
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10522485/
Abstract

Presentation of antigenic peptides by major histocompatibility complex class II (MHC-II) proteins determines T helper cell reactivity. The MHC-II genetic locus displays a large degree of allelic polymorphism influencing the peptide repertoire presented by the resulting MHC-II protein allotypes. During antigen processing, the human leukocyte antigen (HLA) molecule HLA-DM (DM) encounters these distinct allotypes and catalyzes exchange of the placeholder peptide CLIP by exploiting dynamic features of MHC-II. Here, we investigate 12 highly abundant CLIP-bound HLA-DRB1 allotypes and correlate dynamics to catalysis by DM. Despite large differences in thermodynamic stability, peptide exchange rates fall into a target range that maintains DM responsiveness. A DM-susceptible conformation is conserved in MHC-II molecules, and allosteric coupling between polymorphic sites affects dynamic states that influence DM catalysis. As exemplified for rheumatoid arthritis, we postulate that intrinsic dynamic features of peptide-MHC-II complexes contribute to the association of individual MHC-II allotypes with autoimmune disease.

摘要

主要组织相容性复合体 II 类 (MHC-II) 蛋白呈递抗原肽决定了 T 辅助细胞的反应性。MHC-II 遗传位点显示出很大程度的等位基因多态性，影响由此产生的 MHC-II 蛋白同种型所呈现的肽库。在抗原加工过程中，人类白细胞抗原 (HLA) 分子 HLA-DM (DM) 遇到这些不同的同种型，并利用 MHC-II 的动态特性催化占位肽 CLIP 的交换。在这里，我们研究了 12 种高度丰富的 CLIP 结合 HLA-DRB1 同种型，并将动力学与 DM 的催化作用相关联。尽管热力学稳定性存在很大差异，但肽交换率落入维持 DM 反应性的目标范围内。DM 敏感构象在 MHC-II 分子中保守，多态性位点之间的变构偶联影响影响 DM 催化的动态状态。以类风湿关节炎为例，我们假设肽-MHC-II 复合物的固有动态特征有助于将个体 MHC-II 同种型与自身免疫性疾病相关联。

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2
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3
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Nat Biotechnol. 2024 Dec 13. doi: 10.1038/s41587-024-02466-y.
4
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