Stability and diversity of T cell receptor repertoire usage during lymphocytic choriomeningitis virus infection of mice.
Stability and diversity of T cell receptor repertoire usage during lymphocytic choriomeningitis virus infection of mice.
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DOI：
10.1084/jem.188.11.1993
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发表时间：
1998-12-07
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许多研究都检查了选定的病毒特异性 T 细胞克隆的 T 细胞受体 (TCR) 使用情况，但关于病毒感染期间 TCR 库使用的稳定性和多样性的信息很少。在这里，我们通过互补决定区 3 (CDR3) 长度谱分型直接离体分析了整个急性淋巴细胞脉络膜脑膜炎病毒 (LCMV) 感染过程中的 Vβ8.1 TCR 库，进入记忆，并在 T 细胞克隆耗尽的条件下。 Vβ8 群体占 LCMV 诱导的 CD8+ T 细胞的 30-35%，并且包括识别多种 LCMV 编码肽的 T 细胞，从而可以全面研究针对复杂抗原的多克隆 T 细胞反应。基因相同的小鼠产生显着不同的 T 细胞反应，这反映在相同大小的光谱类型带中的不同光谱类型和不同 TCR 序列；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 细胞库进化的有意义的研究需要在个体小鼠中进行纵向研究。这种对外周血淋巴细胞样本的纵向研究表明，(a)病毒诱导的T细胞库在病毒抗原清除后的细胞凋亡期间几乎没有变化； (b) LCMV 感染极大地扭曲了宿主 T 细胞的记忆状态； (c) T 细胞库的连续选择发生在持续感染的条件下。
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 Vβ8.1 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 Vβ8 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.