Inhibitory receptor signaling domain

The "inhibitory receptor signaling domain" refers to conserved sequence motifs (e.g., ITIM and ITSM) within the cytoplasmic domains of numerous immune inhibitory receptors, including PD-1, CTLA-4, BTLA, SIRPα, Siglecs, and KIRs[2][5][6]. Upon ligand binding, these domains are phosphorylated and recruit SH2 domain-containing phosphatases such as SHP-1, SHP-2, and SHIP, thereby dephosphorylating key signaling proteins and dampening immune cell activation[2][4][5][6]. These motifs play a central role in immune regulation but do not constitute a unique molecular entity; many different receptors use similar domains to inhibit cell signaling. The domain itself is not the druggable target; rather, the inhibitory receptor as a whole is the therapeutic target[2][5].

Other names

Immunoreceptor tyrosine-based inhibitory motif (ITIM)Immune receptor tyrosine-based switch motif (ITSM)Inhibitory signaling motifInhibitory motif domain