Pre–T cell receptors topologically sample self-ligands during thymocyte β-selection

doi:10.1126/science.abe0918

GSTDTAP > 气候变化

DOI	10.1126/science.abe0918
	Pre–T cell receptors topologically sample self-ligands during thymocyte β-selection
	Xiaolong Li; Réka Mizsei; Kemin Tan; Robert J. Mallis; Jonathan S. Duke-Cohan; Aoi Akitsu; Paul W. Tetteh; Abhinav Dubey; Wonmuk Hwang; Gerhard Wagner; Matthew J. Lang; Haribabu Arthanari; Jia-huai Wang; Ellis L. Reinherz
	2021-01-08
发表期刊	Science
出版年	2021
英文摘要	The T cell receptor (TCR) recognizes peptide-bound major histocompatibility complex molecules (pMHCs) and consists of an α chain in association with a β chain. Both chains have hypervariable complementarity-determining regions (CDRs) that inform whether a particular TCR can recognize a given pMHC. To successfully graduate from the thymus, aspiring αβT cells must generate a functional TCR. During one early checkpoint in this process, the β chain is first paired with a preTβ chain to form the preTCR. Li et al. used x-ray crystallography to visualize how preTCRs recognize pMHCs. They report that the CDR3 loop of the preTCR β chain contacts the pMHC with a distinctive lateral topography. This is in contrast to the established binding modality of mature TCRs, whereby all three CDR loops on both α and β chains bind in a vertical orientation. These complexes help solve the mystery of how only functionally rearranged β chains using competent CDR3 loops can properly engage with pMHC at the preTCR stage. Science , this issue p. [181][1] Self-discrimination, a critical but ill-defined molecular process programmed during thymocyte development, requires myriad pre–T cell receptors (preTCRs) and αβTCRs. Using x-ray crystallography, we show how a preTCR applies the concave β-sheet surface of its single variable domain (Vβ) to “horizontally” grab the protruding MHC α2-helix. By contrast, αβTCRs purpose all six complementarity-determining region (CDR) loops of their paired VαVβ module to recognize peptides bound to major histocompatibility complex molecules (pMHCs) in “vertical” head-to-head binding. The preTCR topological fit ensures that CDR3β reaches the peptide’s featured C-terminal segment for pMHC sampling, establishing the subsequent αβTCR canonical docking mode. “Horizontal” docking precludes germline CDR1β- and CDR2β-MHC binding to broaden β-chain repertoire diversification before αβTCR-mediated selection refinement. Thus, one subunit successively attunes the recognition logic of related multicomponent receptors. [1]: /lookup/doi/10.1126/science.abe0918
领域	气候变化 ; 资源环境
URL	查看原文
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/310450
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Xiaolong Li,Réka Mizsei,Kemin Tan,等. Pre–T cell receptors topologically sample self-ligands during thymocyte β-selection[J]. Science,2021.
APA	Xiaolong Li.,Réka Mizsei.,Kemin Tan.,Robert J. Mallis.,Jonathan S. Duke-Cohan.,...&Ellis L. Reinherz.(2021).Pre–T cell receptors topologically sample self-ligands during thymocyte β-selection.Science.
MLA	Xiaolong Li,et al."Pre–T cell receptors topologically sample self-ligands during thymocyte β-selection".Science (2021).