Does constant regulation of CD8 T cell functional avidity explain its stability

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 T cell receptor (TCR) affinity, downstream signaling strength and TCR affinity-independent parameters of the immune synapse, such as co-stimulatory and inhibitory receptors. The functional impact of co-receptors 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, co-dominant 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. This article is protected by copyright. All rights reserved.