AI Article Synopsis
- Signal-transducing adaptor protein-2 (STAP-2) aids TCR signaling by binding to CD3ζ ITAMs and enhancing immune responses.
- A synthetic peptide derived from STAP-2 (iSP2) interacts with CD3ζ ITAMs, blocking STAP-2’s activity and inhibiting TCR signaling.
- iSP2's delivery reduces T cell proliferation and IL-2 production, indicating its potential as an immunomodulator in treating autoimmune diseases like experimental autoimmune encephalomyelitis.
Article Abstract
Signal-transducing adaptor protein-2 (STAP-2) is an adaptor protein that contains pleckstrin and Src homology 2-like domains, as well as a proline-rich region in its C-terminal region. Our previous study demonstrated that STAP-2 positively regulates TCR signaling by associating with TCR-proximal CD3ζ ITAMs and the lymphocyte-specific protein tyrosine kinase. In this study, we identify the STAP-2 interacting regions of CD3ζ ITAMs and show that the STAP-2-derived synthetic peptide (iSP2) directly interacts with the ITAM sequence and blocks the interactions between STAP-2 and CD3ζ ITAMs. Cell-penetrating iSP2 was delivered into human and murine T cells. iSP2 suppressed cell proliferation and TCR-induced IL-2 production. Importantly, iSP2 treatment suppressed TCR-mediated activation of naive CD4+ T cells and decreased immune responses in CD4+ T cell-mediated experimental autoimmune encephalomyelitis. It is likely that iSP2 is a novel immunomodulatory tool that modulates STAP-2-mediated activation of TCR signaling and represses the progression of autoimmune diseases.
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| http://dx.doi.org/10.4049/jimmunol.2200942 | DOI Listing |
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