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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)57-68
Number of pages12
JournalJournal of Immunology
Volume209
Issue number1
DOIs
Publication statusPublished - 2022 Jul 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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