The quality of T cell responses depends on the lymphocytes' ability to undergo clonal expansion, acquire effector functions and traffic to the site of infection. Although TCR signal strength is thought to dominantly shape the T cell response, by using TCR transgenic CD4⁺ T cells with different pMHC binding affinity, we reveal that TCR affinity does not control Th1 effector function acquisition nor the functional output of individual effectors following mycobacterial infection. Rather, TCR affinity calibrates the rate of cell division to synchronize the distinct processes of T cell proliferation, differentiation and trafficking. By timing cell division-dependent IL-12R expression, TCR affinity controls when T cells become receptive to Th1-imprinting IL-12 signals, determining the emergence and magnitude of the Th1 effector pool. These findings reveal a distinct yet cooperative role for IL-12 and TCR signalling in Th1 differentiation and suggests that the temporal activation of clones with different TCR affinity is a major strategy to coordinate immune surveillance against persistent pathogens.

中文翻译：

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TCR亲和力控制Th1对分枝杆菌反应的动力学而非功能规格

T细胞反应的质量取决于淋巴细胞进行克隆扩增，获得效应子功能和运输到感染部位的能力。尽管TCR信号强度被认为主要影响T细胞反应，但通过使用TCR转基因CD4 ⁺具有不同pMHC结合亲和力的T细胞，我们揭示了TCR亲和力不控制分枝杆菌感染后Th1效应子的功能获得，也不控制单个效应子的功能输出。相反，TCR亲和力可校准细胞分裂的速率，以同步T细胞增殖，分化和运输的不同过程。通过计时依赖于细胞分裂的IL-12R表达，TCR亲和力控制T细胞何时能够接受印有Th1的IL-12信号，从而确定Th1效应子库的出现和大小。这些发现揭示了IL-12和TCR信号在Th1分化中的独特而协同的作用，并表明具有不同TCR亲和力的克隆的暂时激活是协调针对持久性病原体的免疫监视的主要策略。