Immunoglobulin-like receptors are members of the immunoglobulin superfamily and have one or more 70-110 residue immunoglobulin domains (Ig) in their extracellular region, typically multiple such domains in tandem. Many of the genes encoding these proteins occur in the leukocyte receptor complex (LRC), a large gene cluster on human chromosome 19. Members of this group found in the human genome include:
* The killer-cell immunoglobulin-like receptor (KIR) family contains proteins with 2-3 extracellular Ig domains and long (inhibitory) or short (activating) cytoplasmic regions. Typically expressed in NK and some T cells, they interact with MHC class I. This gene family located in the LRC is highly polymorphic and there is individual variation in both alleles and copy number, as well as in alternative splicing. This family has undergone significant diversification in primate lineages.
* The leukocyte immunoglobulin-like receptors (LILR) family contains 13 genes, including two pseudogenes. They have 2-4 Ig domains. One member, LILRA3, lacks a transmembrane region and is a soluble protein; others may be expressed in soluble form through alternative splicing. Like the similar KIR family, LILR genes are found in the LRC and are polymorphic, though less so than KIR. LILR proteins are broadly expressed in immune cells and have very diverse ligands.
* The paired type 2 immunoglobulin like receptor (PILR) family contains two genes, PILRA (inhibiting) and PILRB (activating). They have a single extracellular Ig domain with a siglec-like structure.
* The signal regulatory protein (SIRP) family contains three genes, SIRPA (inhibiting), SIRPB1 (activating), and SIRPG (non-signaling), with the more distantly related SIRPD and SIRPB2 not yet well characterized. SIRPA interacts with CD47, a regulator of phagocytosis. This family also interacts with surfactant protein D.
* The carcinoembryonic antigen-related cell adhesion (CEACAM) family contains 12 genes with one or more Ig domains. They are expressed broadly, especially in endothelium and epithelium and have roles in cell-cell recognition. They have been extensively studied for their role in cancer and have been used as cancer biomarkers.
* The siglec family contains 15 genes divided into two evolutionarily related groups. This family has three members with activating motifs, Siglec-14, Siglec-15, and Siglec-16. These proteins bind sialic acids, and are often targeted by pathogens.
* TIGIT (T cell immunoreceptor with Ig and ITIM domains) is an inhibitory receptor that forms a nonhomologous but functional pair with DNAM1 (CD226).