QRICH1 mediates an intracellular checkpoint for CD8 + T cell activation via the CARD11 signalosome
细胞内
细胞生物学
生物
化学
生物物理学
作者
Nicole Carter,Wihib D. Hankore,Yongkang Yang,Chao Yang,Shelby M. Hutcherson,Wyatt Fales,Anushka Ghosh,Piyusha Mongia,Sophie Mackinnon,Anna Marie Brennan,Robert D. Leone,Joel L. Pomerantz
出处
期刊:Science immunology [American Association for the Advancement of Science (AAAS)] 日期:2025-03-14卷期号:10 (105)
标识
DOI:10.1126/sciimmunol.adn8715
摘要
Antigen receptor signaling pathways that control lymphocyte activation depend on signaling hubs and negative regulatory proteins to fine-tune signaling outputs to ensure host defense and avoid pathogenic responses. Caspase recruitment domain–containing protein 11 (CARD11) is a critical signaling scaffold that translates T cell receptor (TCR) triggering into the activation of nuclear factor κB (NF-κB), c-Jun N-terminal kinase (JNK), mechanistic target of rapamycin (mTOR), and Akt. Here, we identify glutamine-rich protein 1 (QRICH1) as a regulator of CARD11 signaling that mediates an intracellular checkpoint for CD8 + T cell activation. QRICH1 associates with CARD11 after TCR engagement and negatively regulates CARD11 signaling to NF-κB. QRICH1 binding to CARD11 is controlled by an autoregulatory intramolecular interaction between QRICH1 domains of previously uncharacterized function. QRICH1 controls the antigen-induced activation, proliferation, and effector status of CD8 + T cells by regulating numerous genes critical for CD8 + T cell function. Our results define a component of antigen receptor signaling circuitry that fine-tunes effector output in response to antigen recognition.