| Description |
Two major cell types of the adaptive immune system, CD4+ and CD8+ T cells, express a T cell receptor (TCR) that confers antigen specificity and is responsible for initiating cellular activation. The TCR imparts influence on the cellular fate of T cells not only through the signals that perpetuate from its binding to its cognate antigen but also through the binding interactions of that interface. Here we find a direct effect of TCR signal strength on effector and memory differentiation of anti-viral CD4+ T cells. Following initial antigen encounter and cellular activation, increased TCR signals in CD4+ T cells promote terminal Th1 effector differentiation while lower TCR signals instigate Tfh and memory differentiation. This further supports the theory that CD4+ T cells receive the appropriate signals required for memory differentiation early during an immune response. We also show that TCR affinity for tumor antigen dictates the ability of CD8+ T cells to traffic to the tumor and their anti-tumor activity once in the tumor microenvironment. High-affinity TCR-antigen interactions promote greater influx of CD8+ T cells into the tumor than low-affinity counterparts while very low-affinity interactions inhibit any T cell relocation. The anti-tumor activity of CD8+ T cells correlates with their affinity for tumor antigen in that high-affinity interactions impede tumor growth more than their low-affinity counterparts. However, T cell exhaustion markers are elevated in high-affinity CD8+ T cells compared to mid- to low-affinity T ABSTRACT iv cells, suggesting an optimal tumor antigen affinity for CD8+ T cells to promote not only tumor trafficking but also sustained anti-tumor activity. |
