Alternative titles; symbols
HGNC Approved Gene Symbol: KIR2DL2
Cytogenetic location: 19q13.4 Genomic coordinates (GRCh38): 19:50,900,001-58,617,616
For background information on the KIR family of natural killer (NK) cell Ig-like receptors, see KIR2DL1 (604936).
By screening NK cells with a KIR2DL3 (604938) cDNA probe, Wagtmann et al. (1995) isolated a KIR2DL2 cDNA, which they called clone 43 (CL43), encoding a deduced 348-amino acid type I transmembrane protein. Sequence analysis revealed a structure similar to that described for KIR2DL1, with 2 extracellular C2-type Ig-like domains, a transmembrane domain, and a long cytoplasmic tail with 2 ITIMs (immunoreceptor tyrosine-based inhibitory motifs). Dohring et al. (1996) also identified KIR2DL2, which they termed NKAT6.
By analysis of somatic cell hybrids, Colonna and Samaridis (1995) and Wagtmann et al. (1995) mapped the KIR gene family to chromosome 19.
Human leukocyte antigen (HLA)-C (142840) molecules regulate the function of natural killer cells and may be divided into groups, C(1) and C(2), based on their specificity for inhibitory killer immunoglobulin-like receptors. HLA-C(1) alleles are ligands for KIR2DL2/3, whereas HLA-C(2) alleles are recognized by KIR2DL1. Giebel et al. (2005) analyzed the impact of the HLA-C genotype on outcome of HLA-C-matched unrelated donor hematopoietic stem cell transplantation (URD-HSCT) recipients. HLA-C(2) homozygous patients (n = 18) had lower probability of overall survival (P = 0.01) and disease-free survival (P = 0.02), resulting from increased relapse rate (P = 0.02) when compared with both HLA-C(1) homozygous (n = 43) and HLA-C(1)/C(2) heterozygous (n = 50) subgroups. Patients lacking HLA-C(1) appeared to have an increased risk of relapse following HLA-C-matched URD-HSCT.
Jennes et al. (2006) genotyped HLA and KIR alleles in human immunodeficiency virus (HIV; see 609423)-exposed seronegative female sex workers (FSWs), HIV-seropositive FSWs, and HIV-seronegative female blood donors from Abidjan, Cote d'Ivoire. HIV-exposed seronegative FSWs had an increased frequency of inhibitory KIR genes in the absence of their cognate HLA genes: KIR2DL2/KIR2DL3 heterozygosity in the absence of HLA-C1, and KIR3DL1 homozygosity in the absence of HLA-Bw4 (see 142830). In contrast, HIV-seropositive FSWs were characterized by corresponding KIR/HLA pairings: KIR2DL3 homozygosity with HLA-C1 and a trend toward KIR3DL1/HLA-Bw4 homozygosity. Jennes et al. (2006) proposed that a lack of inhibitory KIRs may lower the threshold for NK-cell activation and that NK cells and KIR/HLA interactions may be important in antiviral immunity.
Although nearly all adults have been exposed to herpes simplex virus (HSV)-1, the clinical course of infection varies remarkably. By analyzing the contribution of gene families on chromosomes 1, 6, 12, and 19 to susceptibility to HSV-1 infection in 302 individuals, Moraru et al. (2012) identified no specific susceptibility locus. However, they found that the risk of suffering clinical HSV-1 infection was modified by MHC class I allotypes, HLA-C1 interaction with KIR2DL2, and the phe/val polymorphism at codon 158 of CD16A (FCGR3A; 146740).
By genotyping individuals from 30 distinct populations, Single et al. (2007) detected strong negative correlations between the presence of activating KIR genes and their corresponding HLA ligand groups across populations. Weak positive relationships, on the other hand, were found between inhibitory KIR genes and their HLA ligands. A negative correlation was observed between distance from East Africa and the frequency of activating KIR genes and their corresponding ligands. Single et al. (2007) concluded that activating, rather than inhibitory, receptor-ligand pairs show the strongest signature of coevolution between the complex KIR and HLA genetic systems.
Colonna, M., Samaridis, J. Cloning of immunoglobulin-superfamily members associated with HLA-C and HLA-B recognition by human natural killer cells. Science 268: 405-408, 1995. [PubMed: 7716543] [Full Text: https://doi.org/10.1126/science.7716543]
Dohring, C., Samaridis, J., Colonna, M. Alternatively spliced forms of human killer inhibitory receptors. Immunogenetics 44: 227-230, 1996. [PubMed: 8662091] [Full Text: https://doi.org/10.1007/BF02602590]
Giebel, S., Locatelli, F., Wojnar, J., Velardi, A., Mina, T., Giorgiani, G., Krawczyk-Kulis, M., Markiewicz, M., Wylezol, I., Halowiecki, J. Homozygosity for human leucocyte antigen-C ligands of KIR2DL1 is associated with increased risk of relapse after human leucocyte antigen-C-matched unrelated donor haematopoietic stem cell transplantation. Brit. J. Haemat. 131: 483-486, 2005. [PubMed: 16281939] [Full Text: https://doi.org/10.1111/j.1365-2141.2005.05797.x]
Jennes, W., Verheyden, S., Demanet, C., Adje-Toure, C. A., Vuylsteke, B., Nkengasong, J. N., Kestens, L. Cutting edge: resistance to HIV-1 infection among African female sex workers is associated with inhibitory KIR in the absence of their HLA ligands. J. Immun. 177: 6588-6592, 2006. [PubMed: 17082569] [Full Text: https://doi.org/10.4049/jimmunol.177.10.6588]
Moraru, M., Cisneros, E., Gomez-Lozano, N., de Pablo, R., Portero, F., Canizares, M., Vaquero, M., Roustan, G., Millan, I., Lopez-Botet, M., Vilches, C. Host genetic factors in susceptibility to herpes simplex type 1 virus infection: contribution of polymorphic genes at the interface of innate and adaptive immunity. J Immun. 188: 4412-4420, 2012. [PubMed: 22490439] [Full Text: https://doi.org/10.4049/jimmunol.1103434]
Single, R. M., Martin, M. P., Gao, X., Meyer, D., Yeager, M., Kidd, J. R., Kidd, K. K., Carrington, M. Global diversity and evidence for coevolution of KIR and HLA. Nature Genet. 39: 1114-1119, 2007. [PubMed: 17694058] [Full Text: https://doi.org/10.1038/ng2077]
Wagtmann, N., Biassoni, R., Cantoni, C., Verdiani, S., Malnati, M. S., Vitale, M., Bottino, C., Moretta, L., Moretta, A., Long, E. O. Molecular clones of the p58 NK cell receptor reveal immunoglobulin-related molecules with diversity in both the extra- and intracellular domains. Immunity 2: 439-449, 1995. [PubMed: 7749980] [Full Text: https://doi.org/10.1016/1074-7613(95)90025-x]