Cell Immunoglobulin-like Receptors (cell + immunoglobulin-like_receptor)

Distribution by Scientific Domains

Kinds of Cell Immunoglobulin-like Receptors

  • killer cell immunoglobulin-like receptor

  • Selected Abstracts

    The KIR and CD94/NKG2 families of molecules in the rhesus monkey

    Michelle L. LaBonte
    Summary: Natural killer (NK) cells and a subset of T cells express families of receptors that are capable of detecting major histocompatibility complex (MHC) class I expression on the surface of cells. Molecules of the killer cell immunoglobulin-like receptor (KIR) family bind directly to MHC class I, while those of the CD94/NKG2 family recognize MHC class I signal sequences bound to HLA-E. Both the KIR and CD94/NKG2 families are composed of activating and inhibitory molecules that serve to regulate the function of NK cells as a result of their MHC class I recognition. Here we review the recently described KIR and CD94/NKG2 family members in the rhesus monkey. [source]

    The genomic context of natural killer receptor extended gene families

    John Trowsdale
    Summary: The two sets of inhibitory and activating natural killer (NK) receptor genes belong either to the Ig or to the C-type lectin superfamilies. Both are extensive and diverse, comprising genes of varying degrees of relatedness, indicative of a process of iterative duplication. We have constructed gene maps to help understand how and when NK receptor genes developed and the nature of their polymorphism. A cluster of over 15 C-type lectin genes, the natural killer complex is located on human chromosome 12p13.1, syntenic with a region in mouse that borders multiple Ly49 loci. The equivalent locus in man is occupied by a single pseudogene, LY49L. The immunoglobulin superfamily of loci, the leukocyte receptor complex (LRC), on chromosome 19q13.4, contains many polymorphic killer cell immunoglobulin-like receptor (KIR) genes as well as multiple related sequences. These include immunoglobulin-like transcript (ILT) (or leukocyte immunoglobulin-like receptor genes), leukocyte-associated inhibitory receptor genes (LAIR), NKp46, Fc,R and the platelet glycoprotein receptor VI locus, which encodes a collagen-binding molecule. KIRs are expressed mostly on NK cells and some T cells. The other LRC loci are more widely expressed. Further centromeric of the LRC are sets of additional loci with weak sequence similarity to the KIRs, including the extensive CD66(CEA) and Siglec families. The LRC-syntenic region in mice contains no orthologues of KIRs. Some of the KIR genes are highly polymorphic in terms of sequence as well as for presence/absence of genes on different haplotypes. Some anchor loci, such as KIR2DL4, are present on most haplotypes. A few ILT loci, such as ILT5 and ILT8, are polymorphic, but only ILT6 exhibits presence/absence variation. This knowledge of the genomic organisation of the extensive NK superfamilies underpins efforts to understand the functions of the encoded NK receptor molecules. It leads to the conclusion that the functional homology of human KIR and mouse Ly49 genes arose by convergent evolution. NK receptor immunogenetics has interesting parallels with the major histocompatibility complex (MHC) in which some of the polymorphic genes are ligands for NK molecules. There are hints of an ancient genetic relationship between NK receptor genes and MHC-paralogous regions on chromosomes 1, 9 and 19. The picture that emerges from both complexes is of eternal evolutionary restlessness, presumably in response to resistance to disease. This work was funded by the Wellcome Trust and the MRC [source]

    Structural basis of MHC class I recognition by natural killer cell receptors

    Mark W. Sawicki
    Summary: Natural killer (NK)-cell function is regulated by NK receptors that recognize MHC class I (MHC-I) molecules on target cells. Two structurally distinct families of NK receptors have been identified, the immunoglobulin-like family (killer cell immunoglobulin-like receptors (KIRs), leukocyte immunoglobulin-like receptors (LIRs)) and the C-type lectin-like family (Ly49, CD94/NKG2A, NKG2D, CD69). Recently, the three-dimensional structures of several NK receptors were determined, in free form or bound to MHC-I. These include those of unbound KIRs, NKG2D, CD69, LIR-1 and the CD94 subunit of the CD94/NKG2A heterodimer. Together, these structures define the basic molecular architecture of both the immunoglobulin-like and C-type lectin-like families of NK receptors. In addition, crystal structures have been reported for the complex between Ly49A and H-2Dd, and for KIR2DL2 bound to HLA-Cw3. The complex structures provide a framework for understanding MHC-I recognition by NK receptors from both families and reveal striking differences in the nature of this recognition, despite the receptors' functional similarity. This research was supported, in part, by National Institutes of Health grants R01 AI47900 and R37 36900 (RAM) and a fellowship from the Cancer Research Institute (MWS). We are grateful to DW Wolan and IA Wilson for providing coordinates of NKG2D prior to publication, and to members of our laboratories for encouragement. [source]

    The extensive polymorphism of KIR genes

    IMMUNOLOGY, Issue 1 2010
    Derek Middleton
    Summary The functions of human natural killer (NK) cells are controlled by diverse families of antigen receptors. Prominent among these are the killer cell immunoglobulin-like receptors (KIR), a family of genes clustered in one of the most variable regions of the human genome. Within this review we discuss the vast polymorphism of the KIR gene complex which rivals that of the human leucocyte antigen (HLA) complex. There are several aspects to this polymorphism. Initially there is presence/absence of individual KIR genes, with four of these genes, termed framework genes, being present in all individuals tested to date, except on those very occasional instances when the gene has been deleted. Within each gene, alleles are present at different frequencies. We provide details of a new website that enables convenient searching for data on KIR gene, allele and genotype frequencies in different populations and show how these frequencies vary in different worldwide populations and the high probability of individuals differing in their KIR repertoire when both gene and allele polymorphism is considered. The KIR genes present in an individual may be classified into A and/or B haplotypes, which respectively have a more inhibitory role or a more activating role on the function of the NK cell. Family studies have been used to ascertain the make-up of these haplotypes, inclusion of allele typing enabling determination of whether one or two copies of a particular gene is present. In addition to genetic diversification the KIR gene complex shows differences at the functional level with different alleles having different protein expression levels and different avidity with their HLA ligand. [source]

    Compound KIR - HLA genotype analyses in the Iranian population by a novel PCR,SSP assay

    N. Tajik
    Summary Natural killer (NK) cells eliminate infected and transformed cells while still are self-tolerant. Interactions of the independently segregating Killer cell immunoglobulin-like receptors (KIR) and human leucocyte antigens (HLA) loci play a critical role in NK cell regulation. Different compound KIR-HLA genotypes can impart different thresholds of activation to the NK-cell repertoire and such genotypic variation has been found to confer altered risk in a number of human diseases including viral infections, autoimmune disorders, reproduction abnormalities and cancers. In this study, we presented a novel combined KIR-HLA polymerase chain reaction,sequence-specific primers genotyping assay for simultaneous determination of KIR genes and their three major HLA class I ligand groups (C1, C2, and Bw4). Moreover, known inhibitory and activating KIR + HLA (iKIR + HLA: 2DL2/3 + C1, 2DL1 + C2, 3DL1 + Bw4; and aKIR + HLA: 2DS2 + C1, 2DS1 + C2, 3DS1 + Bw4) combinations as well as co-inheritance of aKIR genes and iKIR + HLA pairs were analysed in a total of 200 unrelated healthy Iranian individuals. All tested subjects had at least one of the three iKIR + HLA pairs and the frequencies of various inhibitory combinations in the study group were: 31.5%, three iKIR + HLA pairs, 53.5%, two iKIR + HLA pairs, and 15%, 0ne iKIR + HLA pair. Furthermore, we revealed that majority of Iranians (69%) carry compound genotypes with greater number of inhibitory pairings than activating combinations (iKIR + HLA > aKIR + HLA). Conversely, iKIR + HLA < aKIR (45%) was dominant genotype in the study group. We conclude that selective evolutionary pressure has propensity to maintain KIR-HLA genotypes with more inhibitory combinations to guarantee self-tolerance. In contrast, existence of activating KIR genes without normal endogenous ligands, potentially arms the NK population for competent immunosurveillance and stronger defense against infections. [source]

    Distribution of killer cell immunoglobulin-like receptor genes in Poles

    E. Majorczyk
    Summary Killer cell immunoglobulin-like receptors (KIRs) present on natural killer cells and minor subpopulations of T cells recognize class I human leucocyte antigen (HLA) molecules on the surface of target cells. Humans differ by the presence or absence of some KIR genes on their chromosomes. As KIRs are important for the outcome of tissue transplantation (particularly for haematopoietic stem cell transplantation) and possibly for pregnancy and autoimmune diseases, knowledge of the KIR gene distribution in a given human population is of practical value. Therefore, we tested 363 healthy individuals from Western Poland for the presence or absence of KIR genes. Results are compared with those published for other human populations. KIR gene frequencies in Poles are close to these in other Caucasoids but different from those in Asian and African populations, and particularly distant from those in Australian Aborigines. [source]

    Analysis of candidate genes on chromosome 19 in coeliac disease: an association study of the KIR and LILR gene clusters

    S. J. Moodie
    Summary Coeliac disease is strongly heritable, with more than half of the genetic susceptibility estimated to come from genes outside the HLA region. Several candidate regions have been suggested from genome-wide linkage studies including chromosome 19q13.4 where linkage has been replicated between populations. The natural killer (NK) cell immunoglobulin-like receptors (KIRs) and leukocyte immunoglobulin-like receptor (LILR, also known as ILT and LIR) gene clusters lie within this region in the leukocyte receptor cluster (LRC). KIR molecules are involved in cytotoxic lymphocyte function and expressed by intraepithelial T and NK cells in the duodenum. We studied 132 unrelated UK Caucasian coeliac patients and their parents together with a control group of 171 UK Caucasians. PCR-SSP for KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL5, LILRA3 (ILT6), LILRA3 deletion and an LILRA3 exon 3 single nucleotide polymorphism (SNP) allowed classification of KIR genotypes into five categories and determination of homozygosity or heterozygosity for the common A and B type KIR haplotypes (as defined in the text) and for the LILRA3 deletion. Case,control analysis found no association of the five KIR genotype categories, the A or B KIR haplotypes, the LILRA3 gene deletion or the LILRA3 exon 3 SNP with coeliac disease. A transmission disequilibrium test also found no association of the A and B KIR haplotypes or the LILRA3 gene deletion with coeliac disease. [source]

    ORIGINAL ARTICLE: Activating Killer Cell Immunoglobulin-Like Receptor Genes' Association with Recurrent Miscarriage

    Rafael Gustavo Vargas
    Problem, Natural killer (NK) cells are regulated through NK cell receptors such as killer cell immunoglobulin-like receptors (KIRs). KIRs are suspected of being involved in the causes of recurrent miscarriage (RM) as a higher proportion of activated NK cells were observed in women with RM when compared with that in controls. The aim of this study was to investigate if KIR genes coding for receptors known to have as ligands HLA class I molecules are correlated with RM. Method of study A matched case,control study was carried out in 68 south Brazilian Caucasian patient couples with RM and 68 control fertile couples. KIR genes were typed by PCR-Reverse SSO method. Results The rate of possession of an elevated number of activating KIR genes (positive for five or six activating KIR genes out of six different activating KIR genes analyzed) in RM patient women was significantly higher (P = 0.0201) when compared with that in control fertile women. These data suggest that women carrying a high content of activating KIR genes have about threefold increased probability to develop RM [OR = 2.71; 95% CI (1.23,6.01)]. Conclusion Our results indicate that RM could be associated with NK cell activation mediated by a profile rich in activating KIR genes. [source]