Tracking phenotypically and functionally distinct T cell subsets via T cell repertoire diversity
Tracking phenotypically and functionally distinct T cell subsets via T cell repertoire diversity
复制标题
DOI：
10.1016/j.molimm.2006.05.017
复制
发表时间：
2008-02-01
影响因子：
3.6
通讯作者：
Doherty, Peter C.
中科院分区：
文献类型：
--
作者：
Kedzierska, Katherine;La Gruta, Nicole L.;Doherty, Peter C.
抗原特异性T细胞受体（TCR）识别免疫原性肽（p）和主要组织相容性复合物（MHC）糖蛋白的复合物。应答T细胞群体显示出对一个或几个TCRP链的偏好使用（或偏倚）的概况。在TCR α链使用中也观察到这种偏斜，尽管不太常见。通过TCRVP和/或TCRV α CDR 3环的序列分析，可以确定单个抗原特异性T细胞组内克隆多样性的程度和特征。本综述提供了这样的TCR库的突出反应，急性和持续性病毒的例子。结构约束和抗原剂量的决定作用进行了讨论，是功能和表型不同的人群可以在克隆水平上定义的方式。此外，“高”与“低”亲合力或“中枢”与“效应器”记忆集的克隆解剖提供了对这些抗原特异性T细胞应答如何产生和维持的见解。由于TCR多样性潜在地影响CD 8（+）T细胞的保护能力和导致病毒逃逸的免疫控制的破坏，因此分析TCR选择和维持的谱对于改善T细胞反应性和效应器功能的功能功效具有意义。(c)2007爱思唯尔有限公司版权所有。
Antigen-specific T cell receptors (TCRs) recognise complexes of immunogenic peptides (p) and major histocompatibility complex (MHC) glycoproteins. Responding T cell populations show profiles of preferred usage (or bias) toward one or few TCRP chains. Such skewing is also observed, though less commonly, in TCR alpha chain usage. The extent and character of clonal diversity within individual, antigen-specific T cell sets can be established by sequence analysis of the TCRVP and/or TCRV alpha CDR3 loops. The present review provides examples of such TCR repertoires in prominent responses to acute and persistent viruses. The determining role of structural constraints and antigen dose is discussed, as is the way that functionally and phenotypically distinct populations can be defined at the clonal level. In addition, clonal dissection of "high" versus "low" avidity, or "central" versus "effector" memory sets provides insights into how these antigen specific T cell responses are generated and maintained. As TCR diversity potentially influences both the protective capacity of CD8(+) T cells and the subversion of immune control that leads to viral escape, analysing the spectrum of TCR selection and maintenance has implications for improving the functional efficacy of T cell responsiveness and effector function. (c) 2007 Elsevier Ltd. All rights reserved.