iSP2 is a peptide derived from residues of signal-transducing adaptor protein-2 (STAP-2) identified as interacting with cluster of differentiation 3 zeta (CD3zeta) immunoreceptor tyrosine based activation motifs (ITAMs) conjugated to octa-arginine to enhance cell penetrating ability. STAP-2 is an adaptor protein that positively regulates T-cell receptor (TCR) signaling by associating with TCR proximal CD3zeta ITAMs and lymphocyte-specific protein tyrosine kinase. iSP2 directly interacts with the ITAM sequence and competitively inhibits STAP-2 - CD3zeta ITAMs interaction and decreases TCR activation in human and murine T cells. In murine models of experimental autoimmune encephalomyelitis, iSP2 significantly suppresses disease development, to a similar extent to that seen in STAP-2 knockout mice.
