Lin M Y, Welsh R M
Department of Pathology and Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
J Exp Med. 1998 Dec 7;188(11):1993-2005. doi: 10.1084/jem.188.11.1993.
Numerous studies have examined T cell receptor (TCR) usage of selected virus-specific T cell clones, yet little information is available regarding the stability and diversity of TCR repertoire usage during viral infections. Here, we analyzed the Vbeta8.1 TCR repertoire directly ex vivo by complementarity-determining region 3 (CDR3) length spectratyping throughout the acute lymphocytic choriomeningitis virus (LCMV) infection, into memory, and under conditions of T cell clonal exhaustion. The Vbeta8 population represented 30-35% of the LCMV-induced CD8(+) T cells and included T cells recognizing several LCMV-encoded peptides, allowing for a comprehensive study of a multiclonal T cell response against a complex antigen. Genetically identical mice generated remarkably different T cell responses, as reflected by different spectratypes and different TCR sequences in same sized spectratype bands; however, a conserved CDR3 motif was found within some same sized bands. This indicated that meaningful studies on the evolution of the T cell repertoire required longitudinal studies within individual mice. Such longitudinal studies with peripheral blood lymphocyte samples showed that (a) the virus-induced T cell repertoire changes little during the apoptosis period after clearance of the viral antigens; (b) the LCMV infection dramatically skews the host T cell repertoire in the memory state; and (c) continuous selection of the T cell repertoire occurs under conditions of persistent infections.
众多研究已对选定的病毒特异性T细胞克隆的T细胞受体（TCR）使用情况进行了检测，但关于病毒感染期间TCR库使用的稳定性和多样性的信息却很少。在此，我们通过互补决定区3（CDR3）长度谱型分析，直接对急性淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染全过程、记忆期以及T细胞克隆耗竭条件下的离体Vbeta8.1 TCR库进行了分析。Vbeta8群体占LCMV诱导的CD8(+) T细胞的30 - 35%，包括识别几种LCMV编码肽的T细胞，从而能够对针对复杂抗原的多克隆T细胞反应进行全面研究。基因相同的小鼠产生了显著不同的T细胞反应，这在相同大小谱型条带中的不同谱型和不同TCR序列中得到体现；然而，在一些相同大小的条带中发现了保守的CDR3基序。这表明对T细胞库进化进行有意义的研究需要在个体小鼠内进行纵向研究。对外周血淋巴细胞样本的此类纵向研究表明：（a）病毒诱导的T细胞库在病毒抗原清除后的凋亡期变化很小；（b）LCMV感染在记忆状态下极大地扭曲了宿主T细胞库；（c）在持续感染条件下会持续发生T细胞库的选择。
