Biology:KIR3DL2

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

Killer cell immunoglobulin-like receptor 3DL2 is a protein that in humans is encoded by the KIR3DL2 gene.

Structure

Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed on natural killer (NK) cells and subsets of T cells. KIR proteins are classified based on the number of extracellular immunoglobulin (Ig) domains—either two (2D) or three (3D)—and the length of their cytoplasmic tails: long (L) or short (S).

KIR3DL2 is a member of the 3DL family, containing three Ig-like domains and a long cytoplasmic tail. The long tail includes one or more immune tyrosine-based inhibitory motifs (ITIMs), which mediate inhibitory signaling upon ligand engagement. In contrast, KIRs with short cytoplasmic tails lack ITIMs and instead signal through association with TYRO protein tyrosine kinase binding protein, resulting in activating signals.

The KIR genes are polymorphic and highly homologous, clustered on chromosome 19q13.4 within the 1 Mb leukocyte receptor complex (LRC). The gene content of this cluster varies among haplotypes, but several "framework" genes—including KIR3DL2—are found in all haplotypes.

Function

KIR3DL2 is involved in the regulation of innate immune responses, primarily through its expression on NK cells and γδ T cells, a subset of non-MHC-I-restricted T cells.

The ligand for KIR3DL2 includes subsets of HLA class I molecules, and interaction with these ligands typically transduces inhibitory signals that suppress NK cell-mediated cytotoxicity. In addition, the protein IGSF8 (Immunoglobulin superfamily member 8) has been identified as a binding partner of KIR3DL2. Engagement of KIR3DL2 by IGSF8 functions as an immune checkpoint that inhibits NK cell cytotoxic activity, highlighting its role in immune evasion mechanisms in cancer.

See also

• Cluster of differentiation

Further reading

• "Molecular clones of the p58 NK cell receptor reveal immunoglobulin-related molecules with diversity in both the extra- and intracellular domains". Immunity 2 (5): 439–449. May 1995. doi:10.1016/1074-7613(95)90025-X. PMID 7749980. 
• "A human killer inhibitory receptor specific for HLA-A1,2". Journal of Immunology 156 (9): 3098–3101. May 1996. doi:10.4049/jimmunol.156.9.3098. PMID 8617928. 
• "The natural killer cell receptor specific for HLA-A allotypes: a novel member of the p58/p70 family of inhibitory receptors that is characterized by three immunoglobulin-like domains and is expressed as a 140-kD disulphide-linked dimer". The Journal of Experimental Medicine 184 (2): 505–518. August 1996. doi:10.1084/jem.184.2.505. PMID 8760804. 
• "Killer cell inhibitory receptors specific for HLA-C and HLA-B identified by direct binding and by functional transfer". Immunity 3 (6): 801–809. December 1995. doi:10.1016/1074-7613(95)90069-1. PMID 8777725. 
• "Human diversity in killer cell inhibitory receptor genes". Immunity 7 (6): 753–763. December 1997. doi:10.1016/S1074-7613(00)80394-5. PMID 9430221. 
• "Diversity of the p70 killer cell inhibitory receptor (KIR3DL) family members in a single individual". Molecules and Cells 10 (1): 54–60. February 2000. doi:10.1007/s10059-000-0054-0. PMID 10774747. 
• "Lipopolysaccharide stimulates the proliferation of human CD56+CD3- NK cells: a regulatory role of monocytes and IL-10". Journal of Immunology 165 (1): 139–147. July 2000. doi:10.4049/jimmunol.165.1.139. PMID 10861046. 
• "Different NK cell surface phenotypes defined by the DX9 antibody are due to KIR3DL1 gene polymorphism". Journal of Immunology 166 (5): 2992–3001. March 2001. doi:10.4049/jimmunol.166.5.2992. PMID 11207248. 
• "Allelic polymorphism synergizes with variable gene content to individualize human KIR genotype". Journal of Immunology 168 (5): 2307–2315. March 2002. doi:10.4049/jimmunol.168.5.2307. PMID 11859120. 
• "DNA methylation maintains allele-specific KIR gene expression in human natural killer cells". The Journal of Experimental Medicine 197 (2): 245–255. January 2003. doi:10.1084/jem.20021127. PMID 12538663. 
• "Assessment of killer cell immunoglobulinlike receptor expression and corresponding HLA class I phenotypes demonstrates heterogenous KIR expression independent of anticipated HLA class I ligands". Human Immunology 64 (2): 183–193. February 2003. doi:10.1016/S0198-8859(02)00802-9. PMID 12559621. 
• "Functional and molecular characterization of a KIR3DL2/p140 expressing tumor-specific cytotoxic T lymphocyte clone infiltrating a human lung carcinoma". Oncogene 22 (46): 7192–7198. October 2003. doi:10.1038/sj.onc.1206627. PMID 14562047. 
• "Activation of a subset of human NK cells upon contact with Plasmodium falciparum-infected erythrocytes". Journal of Immunology 171 (10): 5396–5405. November 2003. doi:10.4049/jimmunol.171.10.5396. PMID 14607943. 
• "Investigation of killer cell immunoglobulin-like receptor gene diversity V. KIR3DL2". Tissue Antigens 64 (3): 226–234. September 2004. doi:10.1111/j.1399-0039.2004.00272.x. PMID 15304002. 
• "Investigation of killer cell immunoglobulin-like receptors gene KIR3DL2 diversity and confirmation of KIR3DL2*015 in a Chinese population". Tissue Antigens 68 (3): 220–224. September 2006. doi:10.1111/j.1399-0039.2006.00651.x. PMID 16948642. 
• "[KIR3DL2: a new step for the management of patients with Sezary syndrome]". Médecine/Sciences 22 (8–9): 691–693. 2006. doi:10.1051/medsci/20062289691. PMID 16962036. 
• "KIR3DL2: diversity in a hematopoietic stem cell transplant population". Tissue Antigens 70 (3): 228–232. September 2007. doi:10.1111/j.1399-0039.2007.00880.x. PMID 17661911. 

This article incorporates text from the United States National Library of Medicine, which is in the public domain.