Thymic progenitors of TCRαβ⁺ CD8αα intestinal intraepithelial lymphocytes require RasGRP1 for development.

ABSTRACT: Strong T cell receptor (TCR) signaling largely induces cell death during thymocyte development, whereas weak TCR signals induce positive selection. However, some T cell lineages require strong TCR signals for differentiation through a process termed agonist selection. The signaling relationships that underlie these three fates are unknown. RasGRP1 is a Ras activator required to transmit weak TCR signals leading to positive selection. Here, we report that, despite being dispensable for thymocyte clonal deletion, RasGRP1 is critical for agonist selection of TCRαβ⁺CD8αα intraepithelial lymphocyte (IEL) progenitors (IELps), even though both outcomes require strong TCR signaling. Bim deficiency rescued IELp development in RasGRP1^-/- mice, suggesting that RasGRP1 functions

SUBMITTER: Golec DP 

PROVIDER: S-EPMC5551581 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature