Anatomic partitioning regulates TCR-pMHC interaction and memory T cell development during early immune contraction phase

Abstract As virus is cleared, immune cells rapidly undergo contraction; however, how cell function and fate are determined during this phase is not yet fully understood. We unexpectedly discovered that during the early immune contraction phase of an acute infection with lymphocytic choriomeningitis virus, the two dimensional TCR–pMHC effective affinity of TCR transgenic P14 T cells was significantly higher for cells from the splenic red pulp (RP) than the white pulp (WP) compartment. This difference in seeing antigen was governed by FoxP3+ regulatory T cells and TGF-beta. Further, memory precursors from WP preferentially developed into long-term memory cells as compared to cells from RP, despite expression of identical cell surface markers. Our results highlight that intricate regulation of T cell function and fate is determined by anatomic partitioning during the early immune contraction phase. These findings could have an important impact on development of more efficient vaccines and T cell-targeted immunotherapy for infectious diseases, cancers, and autoimmune disorders.