LILRB is a member of the leukocyte immunoglobulin-like receptor (LILRs) family, which can be divided into two groups based on different motifs: the inhibitory LILR subfamily B (LILRB1-5) and the activating LILR subfamily A (LILRA1-6).
LILRB belongs to the type I transmembrane glycoprotein, acting as an immune inhibitory receptor. LILRBs are widely expressed in immune cells, osteoclasts, neurons, tumor cells, and can recognize various ligands. LILRBs have various biological functions such as regulating inflammatory responses, immune tolerance, cell differentiation, neuroplasticity, and play essential roles in inflammatory diseases, autoimmune diseases, infectious diseases, neurological disorders, and malignant tumors.
Among the numerous ligands of LILRB1/2, human leukocyte antigen class I (HLA-I) molecules are the most widely expressed. Binding of LILRB1/2 to HLA-I molecules can inhibit antigen-presenting cells, activation of CD8+ T cells, and B cells. Binding of LILRB1 molecules on NK cells to HLA-I molecules can inhibit NK cell cytotoxicity against target cells. Blocking the binding of LILRB1 molecules to HLA-I molecules can restore NK cell cytotoxicity and enhance macrophage phagocytosis of tumor cells. Co-expression of LILRB1/2 and HLA-I molecules on the same cell can regulate mast cell activation and osteoclast development through cis interactions. Due to the numerous membrane surface receptors in the LILRB family, they can serve as important immune checkpoint molecules for tumor immunotherapy.