Figure 2.

Possible route by which heterogeneity of TCR-ligand interactions could propagate through variations in stimulus duration, gene expression, and localization to diversify the T cell response. In this hypothetical situation, antigen affinity affects the frequency and duration of TCR-ligand interactions, the time at which the T cell activates, and expression of genes, including CXCR3. The level of CXCR3 expression then determines whether a cell traffics to the IFR or the middle of the lymph node, where it encounters niche-specific environmental cues that further promote specific differentiation programs. While cartoons in (A) depict a hypothetical “average” cell for each stimulus, those in (B) show putative cellular distributions for (left) experienced stimulation duration and (right) differentiation fate. This is only one of many possible routes that may connect ligand binding to differentiation outcomes. T_SLE, short-lived effector; T_SCM, stem-like memory; T_CM, central memory. Created with Biorender.com.