| First Author | Saitoh K | Year | 2022 |
| Journal | J Immunol | Volume | 209 |
| Issue | 1 | Pages | 57-68 |
| PubMed ID | 35725273 | Mgi Jnum | J:344981 |
| Mgi Id | MGI:7345956 | Doi | 10.4049/jimmunol.2101014 |
| Citation | Saitoh K, et al. (2022) STAP-2 Is a Novel Positive Regulator of TCR-Proximal Signals. J Immunol 209(1):57-68 |
| abstractText | 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 CD3zeta 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. |
