LILRB1, LILRB2, and KIR3DL1 (LILRB1, LILRB2, KIR3DL1)

LILRB1 and LILRB2 are members of the leukocyte immunoglobulin-like receptor (LILR) family, inhibitory receptors expressed mainly on myeloid (LILRB2) and both myeloid/lymphoid (LILRB1) lineages. They feature multiple extracellular immunoglobulin-like domains and cytoplasmic tails containing four ITIMs. Upon ligand (classical/non-classical HLA-I) binding, they suppress intracellular kinase activity and immune cell activation by recruiting phosphatases such as SHP-1/SHP-2. LILRB1 regulates both innate (macrophages, NK cells) and adaptive (T, B cell) immunity. LILRB2 is highly myeloid-restricted and modulates dendritic cell antigen presentation, impacting diseases like HIV-1 infection. KIR3DL1 is a killer cell immunoglobulin-like receptor specifically expressed on NK cells, and inhibits their cytotoxic activity via recognition of HLA-Bw4 alleles. KIR3DL1 is important in transplantation (immune compatibility) and has a diverse range of allelic variants. Collectively, these receptors serve as critical immune "brakes" and are under investigation for therapeutic blockade in cancer and chronic viral infection. All three receptors are structurally defined immunoglobulin-like surface receptors mediating inhibition of immune cells via ITIM-dependent signaling. They act as immune checkpoints, have broad functional implications for tumor immunity, infection, and transplantation, and are emerging targets for antibody-based immunotherapy.

Other names

ILT2CD85jLIR-1ILT4CD85dLIR-2CD158e3DL1

Block ligand (HLA class I, HLA-G, ANGPTL) binding to receptor to inhibit downstream ITIM signaling, release immune inhibition, and restore macrophage or NK cell cytotoxicity. Polarization of macrophages toward anti-tumor phenotype. Impair immune checkpoint function.