LILRBs

LILRBs, or leukocyte immunoglobulin-like receptor B family, are a group of inhibitory receptors belonging to the larger LILR family that regulate immune responses. They are encoded in the LILR gene cluster on chromosome 19 within the leukocyte receptor complex and are expressed on various immune cells. The human repertoire includes five functional receptors, LILRB1 through LILRB5, each with extracytoplasmic immunoglobulin-like domains and a cytoplasmic tail that transmits inhibitory signals.

Ligands for LILRBs are predominantly major histocompatibility complex class I (MHC I) molecules. Classical MHC I molecules (such as HLA-A, -B, and -C) and nonclassical molecules (including HLA-G) can bind several LILRBs, though the strength and specificity of interactions vary among family members. For some LILRBs, ligands beyond classical MHC I are less well defined. Ligand binding generally delivers inhibitory signals that dampen cellular activation and modulate downstream immune responses.

Signaling through LILRBs is mediated by immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in their cytoplasmic tails. Upon ligand engagement, ITIMs recruit phosphatases such as SHP-1 and SHP-2, leading to suppression of activation, cytokine production, antigen presentation, and cytotoxic functions. This inhibitory signaling helps maintain self-tolerance and regulate the intensity and duration of immune responses, particularly in NK cells, dendritic cells, monocytes, and B cells.

Biological and clinical relevance of LILRBs includes roles in maintaining tolerance, shaping anti-tumor and anti-infective immunity, and influencing transplant outcomes. Genetic variation and expression levels of LILRBs have been studied as potential factors in autoimmunity, infection, and cancer, making them of interest as therapeutic targets and biomarkers.