STAP-2 Is a Novel Positive Regulator of TCR-Proximal Signals

Kodai Saitoh, Jun Ichi Kashiwakura, Kota Kagohashi, Yuto Sasaki, Shoya Kawahara, Yuichi Sekine, Yuichi Kitai, Ryuta Muromoto, Michiko Ichii, Hiroko Nakatsukasa, Akihiko Yoshimura, Kenji Oritani, Tadashi Matsuda

研究成果: Article査読

抄録

TCR ligation with an Ag presented on MHC molecules promotes T cell activation, leading to the selection, differentiation, and proliferation of T cells and cytokine production. These immunological events are optimally arranged to provide appropriate responses against a variety of pathogens. We here propose signal-transducing adaptor protein-2 (STAP-2) as a new positive regulator of TCR signaling. STAP-2-deficient T cells showed reduced, whereas STAP-2-overexpressing T cells showed enhanced, TCR-mediated signaling and downstream IL-2 production. For the mechanisms, STAP-2 associated with TCR-proximal CD3f immunoreceptor tyrosine activation motifs and phosphorylated LCK, resulting in enhancement of their binding after TCR stimulation. In parallel, STAP-2 expression is required for full activation of downstream TCR signaling. Importantly, STAP-2-deficient mice exhibited slight phenotypes of CD4+ T-cell-mediated inflammatory diseases, such as experimental autoimmune encephalomyelitis, whereas STAP-2-overexpressing transgenic mice showed severe phenotypes of these diseases. Together, STAP-2 is an adaptor protein to enhance TCR signaling; therefore, manipulating STAP-2 will have an ability to improve the treatment of patients with autoimmune diseases as well as the chimeric Ag receptor T cell therapy.

本文言語English
ページ(範囲)57-68
ページ数12
ジャーナルJournal of Immunology
209
1
DOI
出版ステータスPublished - 2022 7月 1

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学

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