KIR3DL2 explained

Killer cell immunoglobulin-like receptor 3DL2 is a protein that in humans is encoded by the KIR3DL2 gene.^{[1] [2] [3]} The protein IGSF8 (Immunoglobulin superfamily member 8) has been identified as a binding partner of the KIR3DL2 receptor.^[4] Binding of IGSF8 to KIR3DL2 expressed on the surface of natural killer (NK) cells acts as an immune checkpoint that inhibits cytotoxic activity and cell killing by NK cells. KIR3DL2 is highly expressed on both NK cells and γδ T cells (a subtype of non-MHC-I restricted T cells).

Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets of T cells. The KIR genes are polymorphic and highly homologous and they are found in a cluster on chromosome 19q13.4 within the 1 Mb leukocyte receptor complex (LRC). The gene content of the KIR gene cluster varies among haplotypes, although several "framework" genes are found in all haplotypes (KIR3DL3, KIR3DP1, KIR3DL4, KIR3DL2). The KIR proteins are classified by the number of extracellular immunoglobulin domains (2D or 3D) and by whether they have a long (L) or short (S) cytoplasmic domain. KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based inhibitory motif (ITIM), while KIR proteins with the short cytoplasmic domain lack the ITIM motif and instead associate with the TYRO protein tyrosine kinase binding protein to transduce activating signals. The ligands for several KIR proteins are subsets of HLA class I molecules; thus, KIR proteins are thought to play an important role in regulation of the immune response. This gene is one of the "framework" loci that is present on all haplotypes.

See also

• Cluster of differentiation

Further reading

• Wagtmann N, Biassoni R, Cantoni C, etal . Molecular clones of the p58 NK cell receptor reveal immunoglobulin-related molecules with diversity in both the extra- and intracellular domains. . Immunity . 2 . 5 . 439–49 . 1995 . 7749980 . 10.1016/1074-7613(95)90025-X . free .
• Döhring C, Scheidegger D, Samaridis J, etal . A human killer inhibitory receptor specific for HLA-A1,2. . J. Immunol. . 156 . 9 . 3098–101 . 1996 . 10.4049/jimmunol.156.9.3098 . 8617928 .
• Pende D, Biassoni R, Cantoni C, etal . 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. . J. Exp. Med. . 184 . 2 . 505–18 . 1996 . 8760804 . 10.1084/jem.184.2.505 . 2192700 .
• Wagtmann N, Rajagopalan S, Winter CC, etal . Killer cell inhibitory receptors specific for HLA-C and HLA-B identified by direct binding and by functional transfer. . Immunity . 3 . 6 . 801–9 . 1996 . 8777725 . 10.1016/1074-7613(95)90069-1 . free .
• Uhrberg M, Valiante NM, Shum BP, etal . Human diversity in killer cell inhibitory receptor genes. . Immunity . 7 . 6 . 753–63 . 1998 . 9430221 . 10.1016/S1074-7613(00)80394-5 . free .
• Kwon D, Chwae YJ, Choi IH, etal . Diversity of the p70 killer cell inhibitory receptor (KIR3DL) family members in a single individual. . Mol. Cells . 10 . 1 . 54–60 . 2000 . 10774747 . 10.1007/s10059-000-0054-0 . 21075797 . free .
• Goodier MR, Londei M . Lipopolysaccharide stimulates the proliferation of human CD56+CD3- NK cells: a regulatory role of monocytes and IL-10. . J. Immunol. . 165 . 1 . 139–47 . 2000 . 10861046 . 10.4049/jimmunol.165.1.139. free .
• Gardiner CM, Guethlein LA, Shilling HG, etal . Different NK cell surface phenotypes defined by the DX9 antibody are due to KIR3DL1 gene polymorphism. . J. Immunol. . 166 . 5 . 2992–3001 . 2001 . 11207248 . 10.4049/jimmunol.166.5.2992. free .
• Shilling HG, Guethlein LA, Cheng NW, etal . Allelic polymorphism synergizes with variable gene content to individualize human KIR genotype. . J. Immunol. . 168 . 5 . 2307–15 . 2002 . 11859120 . 10.4049/jimmunol.168.5.2307. free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Chan HW, Kurago ZB, Stewart CA, etal . DNA methylation maintains allele-specific KIR gene expression in human natural killer cells. . J. Exp. Med. . 197 . 2 . 245–55 . 2003 . 12538663 . 10.1084/jem.20021127 . 2193817 .
• Becker S, Tonn T, Füssel T, etal . Assessment of killer cell immunoglobulinlike receptor expression and corresponding HLA class I phenotypes demonstrates heterogenous KIR expression independent of anticipated HLA class I ligands. . Hum. Immunol. . 64 . 2 . 183–93 . 2003 . 12559621 . 10.1016/S0198-8859(02)00802-9 .
• Dorothée G, Echchakir H, Le Maux Chansac B, etal . Functional and molecular characterization of a KIR3DL2/p140 expressing tumor-specific cytotoxic T lymphocyte clone infiltrating a human lung carcinoma. . Oncogene . 22 . 46 . 7192–8 . 2003 . 14562047 . 10.1038/sj.onc.1206627 . 23893345 .
• Artavanis-Tsakonas K, Eleme K, McQueen KL, etal . Activation of a subset of human NK cells upon contact with Plasmodium falciparum-infected erythrocytes. . J. Immunol. . 171 . 10 . 5396–405 . 2004 . 14607943 . 10.4049/jimmunol.171.10.5396. free .
• Meenagh A, Williams F, Sleator C, etal . Investigation of killer cell immunoglobulin-like receptor gene diversity V. KIR3DL2. . Tissue Antigens . 64 . 3 . 226–34 . 2005 . 15304002 . 10.1111/j.1399-0039.2004.00272.x .
• Yan LX, Zhu FM, Jiang K, etal . Investigation of killer cell immunoglobulin-like receptors gene KIR3DL2 diversity and confirmation of KIR3DL2*015 in a Chinese population. . Tissue Antigens . 68 . 3 . 220–4 . 2006 . 16948642 . 10.1111/j.1399-0039.2006.00651.x .
• Ortonne N, Bagot M, Bensussan A . [KIR3DL2: a new step for the management of patients with Sezary syndrome] ]. Med Sci (Paris) . 22 . 8–9 . 691–3 . 2006 . 16962036 . 10.1051/medsci/20062289691. free .
• Gedil MA, Steiner NK, Hurley CK . KIR3DL2: diversity in a hematopoietic stem cell transplant population. . Tissue Antigens . 70 . 3 . 228–32 . 2007 . 17661911 . 10.1111/j.1399-0039.2007.00880.x .

Notes and References

1. Colonna M, Samaridis J . Cloning of immunoglobulin-superfamily members associated with HLA-C and HLA-B recognition by human natural killer cells . Science . 268 . 5209 . 405–8 . May 1995 . 7716543 . 10.1126/science.7716543 . 1995Sci...268..405C .
2. Dohring C, Samaridis J, Colonna M . Alternatively spliced forms of human killer inhibitory receptors . Immunogenetics . 44 . 3 . 227–30 . Aug 1996 . 8662091 . 10.1007/BF02602590 . 38478576 .
3. Web site: Entrez Gene: KIR3DL2 killer cell immunoglobulin-like receptor, three domains, long cytoplasmic tail, 2.
4. Li . Yulong . Wu . Xiangyang . Sheng . Caibin . Liu . Hailing . Liu . Huizhu . Tang . Yixuan . Liu . Chao . Ding . Qingyang . Xie . Bin . Xiao . Xi . Zheng . Rongbin . Yu . Quan . Guo . Zengdan . Ma . Jian . Wang . Jin . May 2024 . IGSF8 is an innate immune checkpoint and cancer immunotherapy target . Cell . en . 187 . 11 . 2703–2716.e23 . 10.1016/j.cell.2024.03.039.