Department of Pathology, University of California San Diego, La Jolla, CA 92093.
Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093.
Proc Natl Acad Sci U S A. 2020 Dec 22;117(51):32574-32583. doi: 10.1073/pnas.2013188117. Epub 2020 Dec 7.
It is known that a subpopulation of T cells expresses two T cell receptor (TCR) clonotypes, though the extent and functional significance of this is not established. To definitively evaluate dual TCRα cells, we generated mice with green fluorescent protein and red fluorescent protein reporters linked to TCRα, revealing that ∼16% of T cells express dual TCRs, notably higher than prior estimates. Importantly, dual TCR expression has functional consequences, as dual TCR cells predominated response to lymphocytic choriomeningitis virus infection, comprising up to 60% of virus-specific CD4 and CD8 T cells during acute responses. Dual receptor expression selectively influenced immune memory, as postinfection memory CD4 populations contained significantly increased frequencies of dual TCR cells. These data reveal a previously unappreciated contribution of dual TCR cells to the immune repertoire and highlight their potential effects on immune responses.
已知 T 细胞的一个亚群表达两种 T 细胞受体（TCR）克隆型，尽管其程度和功能意义尚未确定。为了明确评估双重 TCRα 细胞，我们生成了带有绿色荧光蛋白和红色荧光蛋白报告基因的 TCRα 连接的小鼠，结果表明约 16%的 T 细胞表达双重 TCR，明显高于先前的估计。重要的是，双重 TCR 表达具有功能后果，因为双重 TCR 细胞在淋巴细胞性脉络丛脑膜炎病毒感染中占主导地位，在急性反应期间，多达 60%的病毒特异性 CD4 和 CD8 T 细胞是双重 TCR 细胞。双重受体表达选择性地影响免疫记忆，因为感染后记忆性 CD4 群体中双重 TCR 细胞的频率显著增加。这些数据揭示了双重 TCR 细胞对免疫库的先前未被认识到的贡献，并强调了它们对免疫反应的潜在影响。
