LRCH1 deficiency enhances LAT signalosome formation and CD8⁺ T cell responses against tumors and pathogens.

ABSTRACT: CD8⁺ T cells play pivotal roles in eradicating pathogens and tumor cells. T cell receptor (TCR) signaling is vital for the optimal activation of CD8⁺ T cells. Upon TCR engagement, the transmembrane adapter protein LAT (linker for activation of T cells) recruits other key signaling molecules and forms the "LAT signalosome" for downstream signal transduction. However, little is known about which functional partners could restrain the formation of the LAT signalosome and inhibit CD8⁺ cytotoxic T lymphocyte (CTL)-mediated cytotoxicity. Here we have demonstrated that LRCH1 (leucine-rich repeats and calponin homology domain containing 1) directly binds LAT, reduces LAT phosphorylation and interaction with GRB2, and also promotes the endocytosis of LAT. Lrch1</

SUBMITTER: Liu C 

PROVIDER: S-EPMC7431024 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature