T细胞受体基因Tcra和Tcrd的重排过程及其调节机制  

Rearrangement of T cell receptor genes Tcra and Tcrd and its regulatory mechanism

作　　者：朱永常 郝冰涛 Zhu Yongchang;Hao Bingtao(Henan Medical Genetics Institute,Henan Provincial Key Laboratory of Genetic Diseases and Functional Genomics,People′s Hospital of Zhengzhou University,Zhengzhou 450000,China;Cancer Research Institute,School of Basic Medical Sciences,Southern Medical University,Guangzhou 510515,China)

机构地区：[1]郑州大学人民医院,河南省遗传性疾病功能基因组重点实验室,河南省医学遗传研究所,郑州450000 [2]南方医科大学基础医学院,肿瘤研究所,广州510515

出　　处：《中华微生物学和免疫学杂志》2022年第9期737-743,共7页Chinese Journal of Microbiology and Immunology

基　　金：国家自然科学基金(32170885,31970836)。

摘　　要：T细胞受体(T cell receptor,TCR)的高度多样性是其识别抗原的基础,在适应性免疫中发挥重要作用。TCR多样性来自胸腺T细胞发育过程中的V(D)J重排。在4个TCR基因中,Tcra和Tcrd基因位于同一个基因座,共用特定的V基因,因此其重排和调节具有一定的特殊性。抗原受体基因的调控研究主要集中于顺式和反式调控作用。然而,近期的研究表明染色质空间组织在抗原受体基因重排中发挥重要功能。其中染色质组织蛋白质CTCF-Cohesin通过环挤出方式影响重排的效率和TCR组库多样性,而重组酶RAG也可以扫描染色质。本综述描述Tcra和Tcrd基因的重排及其调节机制研究的新进展,特别是染色质空间组织对重排的影响。The high diversity of T cell receptors(TCRs)is the basis for recognizing antigens,playing an essential role in adaptive immunity.TCR diversity is generated from V(D)J rearrangement during the thymocyte development in the thymus.Standing out from the four TCR genes,Tcra and Tcrd genes are characterized by locating at the same locus and sharing specific V genes.Hence,their rearrangement and regulation have a certain particularity.Previous studies mainly focused on cis-regulatory elements and trans-acting factors regulating the Tcra/Tcrd rearrangement.However,recent progress has shown that chromatin spatial organization plays an essential role in antigen receptor gene rearrangement.Chromatin organization proteins,such as CTCF-Cohesin,are involved in regulating rearrangement and enhancing the diversity of TCR repertoire by loop extrusion.Recombinase RAG also scans chromatin of antigen receptor genes for rearrangement.This review described the progress in the rearrangement of Tcra and Tcrd genes and the possible regulatory mechanism,especially the influence of the chromatin spatial organization.

关 键 词：T细胞受体基因 V(D)J重排 染色质构象 CTCF-Cohesin RAG 

分 类 号：R392[医药卫生—免疫学]