Department of Oncology, University Hospital and University of Lausanne, Lausanne, Switzerland.
Eur J Immunol. 2021 Jun;51(6):1348-1360. doi: 10.1002/eji.202049016. Epub 2021 Mar 30.
The functional avidity (FA) of cytotoxic CD8 T cells impacts strongly on their functional capabilities and correlates with protection from infection and cancer. FA depends on TCR affinity, downstream signaling strength, and TCR affinity-independent parameters of the immune synapse, such as costimulatory and inhibitory receptors. The functional impact of coreceptors on FA remains to be fully elucidated. Despite its importance, FA is infrequently assessed and incompletely understood. There is currently no consensus as to whether FA can be enhanced by optimized vaccine dose or boosting schedule. Recent findings suggest that FA is remarkably stable in vivo, possibly due to continued signaling modulation of critical receptors in the immune synapse. In this review, we provide an overview of the current knowledge and hypothesize that in vivo, codominant T cells constantly "equalize" their FA for similar function. We present a new model of constant FA regulation, and discuss practical implications for T-cell-based cancer immunotherapy.
细胞毒性 CD8 T 细胞的功能亲合力（FA）强烈影响其功能能力，并与免受感染和癌症的保护相关。FA 取决于 TCR 亲和力、下游信号转导强度以及免疫突触中 TCR 亲和力非依赖性参数，如共刺激和抑制受体。核心受体对 FA 的功能影响仍有待充分阐明。尽管它很重要，但 FA 很少被评估，也不完全了解。目前对于 FA 是否可以通过优化疫苗剂量或加强免疫时间表来增强还没有共识。最近的研究结果表明，FA 在体内非常稳定，可能是由于免疫突触中关键受体的持续信号调节。在这篇综述中，我们提供了当前知识的概述，并假设在体内，共显性 T 细胞为了实现类似的功能，不断“平衡”它们的 FA。我们提出了一个新的 FA 调节模型，并讨论了其对基于 T 细胞的癌症免疫治疗的实际意义。
