LILRB is a member of the leukocyte immunoglobulin-like receptor (LILR) family, which is 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, serving as an immunoinhibitory receptor. LILRBs are widely expressed in various cells such as immune cells, osteoclasts, nerve cells, and tumor cells, capable of recognizing multiple ligands. LILRBs play various biological functions including regulating inflammatory responses, immune tolerance, cell differentiation, and neural plasticity, and play crucial roles in inflammatory diseases, autoimmune diseases, infectious diseases, neurological disorders, and malignant tumors.
Among the numerous ligands of LILRB1/2, the expression of human leukocyte antigen class I (HLA-I) is most widespread. Binding of LILRB1/2 to HLA-I molecules can inhibit antigen-presenting cells, CD8+ T cells, and B cells activation. When the LILRB1 molecule on the surface of NK cells binds to HLA-I molecules, it can inhibit the killing function of NK cells against target cells. Blocking the binding of LILRB1 molecule to HLA-I molecules can restore the cytotoxic activity of NK cells and enhance the ability of macrophages to engulf 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 presence of numerous membrane surface receptors in the LILRB family, they can serve as important immune checkpoint molecules in tumor immunotherapy.
