德国慕尼黑工业大学Dirk H. Busch和Kilian Schober小组合作取得新进展。他们揭示了在慢性CMV感染过程中，T细胞抗原受体（TCR）向着显性低亲和力克隆的逆向进化。这一研究成果于2020年3月16日在线发表在《自然-免疫学》杂志上。

在该研究中，研究人员探究了巨细胞病毒感染过程中TCR组成部分及其亲和力的进化；巨细胞病毒在人和小鼠中引起大量T细胞产生。使用单细胞和大量TCR测序以及巨细胞病毒特异性T细胞结构亲和力分析并通过生成和监测体内已知的TCR，研究人员发现在慢性感染阶段，高亲和力T细胞克隆的免疫优势下降，这可能是由于细胞衰老所致。这些数据表明，在慢性抗原存在的条件下，低亲和力TCR优先在TCR范围内扩增，这影响免疫治疗的选择。

据介绍，适应性进化是T细胞免疫的重要特征。在急性免疫反应期间，具有高亲和力TCR的T细胞会优先扩增，但仍然未知通过克隆选择获得的亲和力成熟是否会在慢性感染过程中继续存在。

附：英文原文

Title: Reverse TCR repertoire evolution toward dominant low-affinity clones during chronic CMV infection

Author: Kilian Schober, Florian Voit, Simon Grassmann, Thomas R. Mller, Joel Eggert, Sebastian Jarosch, Bianca Weibrich, Patrick Hoffmann, Lisa Borkner, Enzo Nio, Lorenzo Fanchi, Christopher R. Clouser, Aditya Radhakrishnan, Lorenz Mihatsch, Philipp Lckemeier, Justin Leube, Georg Dssinger, Ludger Klein, Michael Neuenhahn, Jennifer D. Oduro, Luka Cicin-Sain, Veit R. Buchholz, Dirk H. Busch

Issue&Volume: 2020-03-16

Abstract: Adaptive evolution is a key feature of T cell immunity. During acute immune responses, T cells harboring high-affinity T cell antigen receptors (TCRs) are preferentially expanded, but whether affinity maturation by clonal selection continues through the course of chronic infections remains unresolved. Here we investigated the evolution of the TCR repertoire and its affinity during the course of infection with cytomegalovirus, which elicits large T cell populations in humans and mice. Using single-cell and bulk TCR sequencing and structural affinity analyses of cytomegalovirus-specific T cells, and through the generation and in vivo monitoring of defined TCR repertoires, we found that the immunodominance of high-affinity T cell clones declined during the chronic infection phase, likely due to cellular senescence. These data showed that under conditions of chronic antigen exposure, low-affinity TCRs preferentially expanded within the TCR repertoire, with implications for immunotherapeutic strategies.

DOI: 10.1038/s41590-020-0628-2

Source: https://www.nature.com/articles/s41590-020-0628-2