Flotillin-2 dampens T cell antigen sensitivity and functionality.

ABSTRACT: T cell receptor (TCR) engagement triggers T cell responses, yet how TCR-mediated activation is regulated at the plasma membrane remains unclear. Here, we report that deleting the membrane scaffolding protein Flotillin-2 (Flot2) increases T cell antigen sensitivity, resulting in enhanced TCR signaling and effector function in response to weak TCR stimulation. T cell-specific Flot2-deficient mice exhibited reduced tumor growth and enhanced immunity to infection. Flot2-null CD4+ T cells exhibited increased Th1 polarization, proliferation, Nur77 induction, and phosphorylation of ZAP70 and ERK1/2 upon weak TCR stimulation, indicating a sensitized TCR-triggering threshold. Single-cell RNA-Seq suggested that Flot2-null CD4+ T cells follow a similar route of activation as WT CD4+ T cells but exhib

SUBMITTER: Moon S 

PROVIDER: S-EPMC11665568 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature