ITIMcontaining

ITIM-containing refers to receptors or proteins that bear Immunoreceptor Tyrosine-based Inhibitory Motifs in their cytoplasmic tails. ITIMs are short sequence motifs that, when the receptor is engaged, undergo phosphorylation at a central tyrosine residue. This phosphorylation creates a binding site for SH2-domain–containing phosphatases such as SHP-1, SHP-2, or SHIP, leading to dephosphorylation of signaling molecules and attenuation of cellular activation. The overall effect is negative regulation of immune cell signaling, helping to maintain tolerance and prevent excessive responses.

Examples of ITIM-containing receptors include inhibitory natural killer (NK) cell receptors from the KIR family, several B and T cell receptors such as CD22 and CD72, leukocyte immunoglobulin-like receptors LILRB1/2/4, and the Fc gamma receptor IIb (CD32b). Some receptors may harbor multiple ITIMs, which can strengthen inhibitory signaling, and others may possess ITIM-like sequences that contribute to regulation. ITIM-containing receptors are often studied alongside receptors that carry different motifs, such as ITSMs (Immunoreceptor Tyrosine-based Switch Motifs), which can mediate distinct signaling outputs.

Biological and clinical relevance centers on setting activation thresholds across immune cell types, including B cells, T cells, NK cells, and myeloid cells. By dampening activation, ITIM-containing receptors contribute to peripheral tolerance, autoimmunity prevention, and control of inflammatory responses. In cancer and transplantation, these inhibitory pathways can influence outcomes, and therapeutic strategies sometimes aim to block ITIM-mediated signals or to modulate their activity in engineered receptors.