Plasticity in the organization and sequences of human KIR/ILT gene families

Wilson, Michael J.; Torkar, Michaela; Haude, Anja; Milne, Sarah; Jones, Tania; Sheer, Denise; Beck, Stephan; Trowsdale, John

doi:10.1073/pnas.080588597

Cited by 578 publications

(705 citation statements)

References 47 publications

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“…Finally, scans of markers within the LRC itself have been complicated by the fact that the complex is constituted by highly homologous duplicated genes (LILR and KIR) variably arranged in tightly packed tandems. 19 The relationship of R-MS with LILRA3 deletion that we have observed is not secondary to association of either with a KIR gene. Nevertheless, an apparent underrepresentation of KIR3DS1 in patients might indicate a minor and independent protective role of KIR haplotypes carrying this gene; or else, it could be a fortuitous result because of the multiple comparisons performed in this study.…”

Section: Association Between Lilra3 Deletion and R-ms In Spanish Patimentioning

confidence: 58%

“…[19][20][21] Of the 17 KIR genes currently recognized, only the two that mark the 5 0 -and 3 0 -ends of the KIR complex are shared by all human genomes, whereas most individuals lack one or more of the other KIR genes. Both the frequency of each KIR gene and the manner in which they combine in haplotypes vary substantially among different populations, variations that have been associated with autoimmune and infectious diseases.…”

Section: Introductionmentioning

confidence: 99%

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Multiple sclerosis associates with LILRA3 deletion in Spanish patients

et al. 2009

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The genetic susceptibility to multiple sclerosis (MS) is only partially explained, and it shows geographic variations. We analyse here two series of Spanish patients and healthy controls and show that relapsing MS (R-MS) is associated with a gene deletion affecting the hypothetically soluble leukocyte immunoglobulin (Ig)-like receptor A3 (LILRA3, 19q13.4), in agreement with an earlier finding in German patients. Our study points to a gene-dose-dependent, protective role for LILRA3, the deletion of which synergizes with HLA-DRB1*1501 to increase the risk of R-MS. We also investigated whether the risk of suffering R-MS might be influenced by the genotypic diversity of killer-cell Ig-like receptors (KIRs), located only B400 kb telomeric to LILRA3, and implicated in autoimmunity and defence against viruses. The relationship of LILRA3 deletion with R-MS is not secondary to linkage disequilibrium with a KIR gene, but we cannot exclude some contributions of KIR to the genetic susceptibility to R-MS.

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Section: Association Between Lilra3 Deletion and R-ms In Spanish Patimentioning

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Multiple sclerosis associates with LILRA3 deletion in Spanish patients

et al. 2009

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“…There are two fully sequenced human KIR haplotypes, each containing nine or 10 KIR genes, but these haplotypes only have four framework KIR in common. 37 Segregation analysis of families suggests that KIR haplotypes can vary widely in gene content with a range of 4-14 genes per haplotype. 38 Why is there so much variation in NK cell receptor repertoires within species?…”

Section: Resultsmentioning

confidence: 99%

Complete elucidation of a minimal class I MHC natural killer cell receptor haplotype

Dewar

Ml³

et al. 2005

Genes Immun

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The BALB/c inbred mouse is widely used in models of infectious disease, transplantation, and cancer. The differences in the immune responses of BALB/c compared to C57BL/6 mice are especially valuable for the identification of immune regulation genes. One striking immune variance between these mice is in the function of natural killer (NK) cells, and there is strong evidence implicating differential expression of Ly49 genes. In this study, the complete BALB/c Ly49 gene cluster has been sequenced and found to contain six functional genes and two pseudogenes. Compared to C57BL/6 mice, there is a 200 kb region absent in the BALB/c cluster including a complete lack of Ly49h-related genes, which explains the increased susceptibility of BALB/c to cytomegalovirus infection. In addition, there is no BALB/c Ly49d allele, explaining the inability of BALB/c NK cells to kill certain tumor cells. The Ly49 region has now been sequenced in three different inbred mouse strains, and comparisons indicate that the evolution of each haplotype is not straightforward and has involved large-scale deletions/ insertions, gene recombination, and unequal crossing over between divergent haplotypes. This study confirms that relatively small murine class I MHC receptor haplotypes exist, analogous to observations made of human killer cell Ig-like receptor gene haplotypes.

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“…[5][6][7][8][9] The KIR2DL4 gene is present on most KIR haplotypes and occurs at a frequency of 100% in most populations, whereas KIR2DL5 is variable among KIR haplotypes and thus differs considerably between populations in its frequency. [10][11][12] Two copies of the KIR2DL5 genes have been characterized, KIR2DL5A and KIR2DL5B, that show 99.5-99.7% identity in their coding sequences. 5 KIR2-DL5A is located in the telomeric half the KIR gene complex whereas the KIR2DL5B is located in the centromeric half.…”

Section: Introductionmentioning

confidence: 99%

“…5 KIR2-DL5A is located in the telomeric half the KIR gene complex whereas the KIR2DL5B is located in the centromeric half. 10,13 Haplotypes carrying both 2DL5A and B have been described, and thus individuals homozygous for these haplotypes may carry four copies of KIR2DL5 sequences. 14 KIR2DL5 displays a variegated distribution on the surface of CD56 dim NK cells, whereas the surface expression of KIR2DL4 appears to be restricted to the minority subset of KIR neg CD56 bright NK cells.…”

Section: Introductionmentioning

confidence: 99%

KIR2DL5 alleles mark certain combination of activating KIR genes

Sharma

Spellman

et al. 2008

Genes Immun

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Killer cell Ig-like receptors (KIR) control the immune response of NK cells and some T cells to infections and tumors. KIR genes evolve rapidly and are variable between individuals in their number, type and sequence. Here, we determined the nature of KIR2DL5 gene polymorphism in four ethnic groups using direct DNA sequencing method. Nine new sequences were discovered. Within the panel of 248 KIR2DL5-positive individuals, 14 KIR2DL5-sequences differing in coding regions were observed. They differed at only seven amino acid positions, and such limited polymorphism is consistent with its conserved nature throughout the hominoid lineage. Ethnic deviation was seen in the distribution of KIR2DL5A, KIR2DL5B and their alleles. African Americans had more KIR2DL5 alleles than other populations indicating that more polymorphisms are yet to be discovered in Africans. Linkage between KIR2DL5-alleles and certain activating-KIR genes were observed, but frequency of these linked clusters differed substantially between populations. Consequently, KIR2DL5 alleles can be used as markers to predict the activating-KIR gene content. Typing system distinguishing A*001 and B*002 alleles can serve as a powerful screening test to assess the content of most variable activating-KIR genes that have been implicated in human disease and in the outcome of hematopoietic stem cell transplantation.

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Plasticity in the organization and sequences of human KIR/ILT gene families

Cited by 578 publications

References 47 publications

Multiple sclerosis associates with LILRA3 deletion in Spanish patients

Multiple sclerosis associates with LILRA3 deletion in Spanish patients

Complete elucidation of a minimal class I MHC natural killer cell receptor haplotype

KIR2DL5 alleles mark certain combination of activating KIR genes

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