Anatomic Compartmentalization Regulates Tcr-Pep-Mhc Interaction And Fate

Whether anatomic location affects T cell function and differentiation has not been defined. Unexpectedly we found, during the early contraction phase of an acute resolving infection with lymphocytic choriomeningitis virus (LCMV) Armstrong, antigen-specific TCR transgenic P14 T cells within the splenic red pulp displayed a higher number of TCR-pMHC bonds (higher affinity) than those from the white pulp when measured by 2D micropipette adhesion frequency assay. This increased bond formation correlated with target cell killing by P14 T cells. Importantly, FoxP3+ regulatory T cells and TGF-β were required to maintain steady levels of TCR-pMHC interactions in the white pulp. Furthermore, memory precursors from the white pulp preferentially developed into long-term memory cells. Our findings highlight anatomic location as a critical regulator of fate and function.