Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets of CD8+ T cells.[3] 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. Alternative splicing results in multiple transcript variants.[2]
The only so far reported ligand of KIR2DL4 is the non-classical HLA class 1 gene HLA-G, leading to the inhibition of the cytolytic NK cell function.[3]
↑Selvakumar A, Steffens U, Dupont B (October 1996). "NK cell receptor gene of the KIR family with two IG domains but highest homology to KIR receptors with three IG domains". Tissue Antigens. 48 (4 Pt 1): 285–94. doi:10.1111/j.1399-0039.1996.tb02647.x. PMID8946682.
↑ 3.03.1Carosella ED, Favier B, Rouas-Freiss N, Moreau P, Lemaoult J (May 2008). "Beyond the increasing complexity of the immunomodulatory HLA-G molecule". Blood. 111 (10): 4862–70. doi:10.1182/blood-2007-12-127662. PMID18334671.
Further reading
Selvakumar A, Steffens U, Dupont B (1997). "Polymorphism and domain variability of human killer cell inhibitory receptors". Immunol. Rev. 155: 183–96. doi:10.1111/j.1600-065X.1997.tb00951.x. PMID9059894.
Selvakumar A, Steffens U, Palanisamy N, Chaganti RS, Dupont B (1997). "Genomic organization and allelic polymorphism of the human killer cell inhibitory receptor gene KIR103". Tissue Antigens. 49 (6): 564–73. doi:10.1111/j.1399-0039.1997.tb02803.x. PMID9234477.
Valiante NM, Uhrberg M, Shilling HG, Lienert-Weidenbach K, Arnett KL, D'Andrea A, Phillips JH, Lanier LL, Parham P (1997). "Functionally and structurally distinct NK cell receptor repertoires in the peripheral blood of two human donors". Immunity. 7 (6): 739–51. doi:10.1016/S1074-7613(00)80393-3. PMID9430220.
Rajalingam R, Gardiner CM, Canavez F, Vilches C, Parham P (2001). "Identification of seventeen novel KIR variants: fourteen of them from two non-Caucasian donors". Tissue Antigens. 57 (1): 22–31. doi:10.1034/j.1399-0039.2001.057001022.x. PMID11169255.
Rajagopalan S, Fu J, Long EO (2001). "Cutting edge: induction of IFN-gamma production but not cytotoxicity by the killer cell Ig-like receptor KIR2DL4 (CD158d) in resting NK cells". J. Immunol. 167 (4): 1877–81. doi:10.4049/jimmunol.167.4.1877. PMID11489965.
Witt CS, Whiteway JM, Warren HS, Barden A, Rogers M, Martin A, Beilin L, Christiansen FT (2002). "Alleles of the KIR2DL4 receptor and their lack of association with pre-eclampsia". Eur. J. Immunol. 32 (1): 18–29. doi:10.1002/1521-4141(200201)32:1<18::AID-IMMU18>3.0.CO;2-7. PMID11754000.
Faure M, Long EO (2002). "KIR2DL4 (CD158d), an NK cell-activating receptor with inhibitory potential". J. Immunol. 168 (12): 6208–14. doi:10.4049/jimmunol.168.12.6208. PMID12055234.
Santourlidis S, Trompeter HI, Weinhold S, Eisermann B, Meyer KL, Wernet P, Uhrberg M (2002). "Crucial role of DNA methylation in determination of clonally distributed killer cell Ig-like receptor expression patterns in NK cells". J. Immunol. 169 (8): 4253–61. doi:10.4049/jimmunol.169.8.4253. PMID12370356.
Becker S, Tonn T, Füssel T, Uhrberg M, Bogdanow M, Seifried E, Seidl C (2003). "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. doi:10.1016/S0198-8859(02)00802-9. PMID12559621.
Gómez-Lozano N, de Pablo R, Puente S, Vilches C (2003). "Recognition of HLA-G by the NK cell receptor KIR2DL4 is not essential for human reproduction". Eur. J. Immunol. 33 (3): 639–44. doi:10.1002/eji.200323741. PMID12616484.
Stewart CA, Van Bergen J, Trowsdale J (2003). "Different and divergent regulation of the KIR2DL4 and KIR3DL1 promoters". J. Immunol. 170 (12): 6073–81. doi:10.4049/jimmunol.170.12.6073. PMID12794136.
Williams F, Maxwell LD, Halfpenny IA, Meenagh A, Sleator C, Curran MD, Middleton D (2003). "Multiple copies of KIR 3DL/S1 and KIR 2DL4 genes identified in a number of individuals". Hum. Immunol. 64 (7): 729–32. doi:10.1016/S0198-8859(03)00089-2. PMID12826375.
Goodridge JP, Witt CS, Christiansen FT, Warren HS (2003). "KIR2DL4 (CD158d) genotype influences expression and function in NK cells". J. Immunol. 171 (4): 1768–74. doi:10.4049/jimmunol.171.4.1768. PMID12902476.