Recognition of HLA‐G by the NK cell receptor KIR2DL4 is not essential for human reproduction

Gómez‐Lozano, Natalia; Pablo, Rosario de; Puente, Sabino; Vilches, Carlos

doi:10.1002/eji.200323741

Cited by 64 publications

(66 citation statements)

References 51 publications

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“…1A). The one negatively reacting gorilla (Shamba) may not have a KIR2DL4 gene, as has been described for rare human donors (45,46). To determine whether this is also a rare phenomenon in gorillas would require analysis of a larger panel of individuals than studied here.…”

Section: Identification Of 11 Gorilla Kirmentioning

confidence: 83%

Domain Shuffling Has Been the Main Mechanism Forming New Hominoid Killer Cell Ig-Like Receptors

Rajalingam

Parham

Abi-Rached

2004

The Journal of Immunology

108

132

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The killer cell Ig-like receptor (KIR) gene family encodes MHC class I-specific receptors, which regulate NK cell responses and are also expressed on subpopulations of T cells. KIR haplotypes vary in gene content, which, in combination with allelic polymorphism, extensively diversifies the KIR genotype both within and between human populations. Species comparison indicates that formation of new KIR genes and loss of old ones are frequent events, so that few genes are conserved even between closely related species. In this regard, the hominoids define a time frame that is particularly informative for understanding the processes of KIR evolution and its potential impact on killer cell biology. KIR cDNA were characterized from PBMC of three gorillas, and genomic DNA were characterized for six additional individuals. Eleven gorilla KIR genes were defined. With attainment of these data, a set of 75 KIR sequences representing five hominoid species was assembled, which also included rhesus monkey, cattle, and rodent KIR. Searching this data set for recombination events, and phylogenetic analysis using Bayesian methods, demonstrated that new KIR were usually the result of recombination between loci in which complete protein domains were shuffled. Further phylogenetic analysis of the KIR sequences after removal of confounding recombined segments showed that only two KIR genes, KIR2DL4 and KIR2DL5, have been preserved throughout hominoid evolution, and one of them, KIR2DL4, is also common to rhesus monkey and hominoids. Other KIR genes represent recombinant forms present in a minority of species, often only one, as exemplified by 8 of the 11 gorilla KIR genes.

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Section: Identification Of 11 Gorilla Kirmentioning

confidence: 83%

Domain Shuffling Has Been the Main Mechanism Forming New Hominoid Killer Cell Ig-Like Receptors

Rajalingam

Parham

Abi-Rached

2004

The Journal of Immunology

108

132

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“…7 Besides point mutation, species acquire new KIR with novel functions more rapidly by asymmetric recombination. This leads, in first place, to haplotypes with gene loss and gene duplication, 14,15 which seem the origin of KIR2DS2 and KIR2DL2, encoded by paralogous genes. When recombination takes place within a gene, the resulting hybrids combine features (binding, signalling and mRNA expression) of the receptors that participated in the recombination.…”

Section: Discussionmentioning

confidence: 99%

Molecular characterisation of KIR2DS2*005, a fusion gene associated with a shortened KIR haplotype

et al. 2011

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KIR2DS2 is an activating homologue of KIR2DL2, an inhibitory killer-cell immunoglobulin-like receptor (KIR) that surveys expression of major histocompatibility complex-C allotypes bearing a C1 epitope. We have studied here its allele KIR2DS2 *005, which shows a hybrid structure-it is identical to other KIR2DS2 alleles in the ectodomain, but has transmembrane and cytoplasmic regions identical to those of KIR2DS3*001, a short-tailed KIR of uncertain expression and function. Our results reveal that KIR2DS2 *005 is a fusion gene-the product of an unequal crossing over by which the genes KIR2DS2 and KIR2DS3 recombined within a 400 base pair region of complete identity in intron 6. Also resulting from that recombination was a shortened KIR haplotype of the B group, in which three genes commonly linked to KIR2DS2 (KIR2DL2, KIR2DL5B and KIR2DS3) are deleted. Population studies indicate that KIR2DS2 *005 is still associated to such haplotype, and it can be found in approximately 1.2% of Caucasoids. Using a combination of two monoclonal antibodies, we also demonstrate that KIR2DS2 *005 encodes a molecule expressed on the surface of natural killer-and T-lymphocytes.

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“…They encode inhibitory KIR with specificity for all three major HLA class I-encoded epitopes, namely KIR2DL1 (HLA-C group 2), KIR2DL3 (HLA-C group 1), and KIR3DL1 (HLA-Bw4). The remaining four KIR genes are shared by both groups and are thus invariably present on all haplotypes (exceptions to this were reported recently [25,26]); these so-called framework genes are KIR3DL3 and KIR3DL2 on the centromeric and telomeric ends, respectively, and KIR3DP1-KIR2DL4 in the central region [9]. Whereas group A haplotypes do not vary in gene content they show extensive variability on the allelic level [27].…”

Section: Two Groups Of Kir Haplotypes: a And Bmentioning

confidence: 93%

The KIR gene family: life in the fast lane of evolution

Uhrberg

2004

Eur J Immunol

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A hallmark of human NK cells is the expression of HLA class I-specific killer-cell immunoglobulin-like receptors (KIR). An interesting facet of the KIR family is the unusual variability of the respective gene cluster, which is changing shape at an astonishing evolutionary pace. Not only do KIR genes come in different allelic variants, but the KIR locus has also gone through drastic contractions and expansions in recent evolutionary history, resulting in a wide variety of KIR haplotypes. A new study now reveals how an originally nonfunctional KIR pseudogene, KIR3DP1, is brought back to life in certain individuals via non-reciprocal recombination between two different KIR haplotypes. This Commentary outlines how the unique architecture of the KIR locus facilitates the generation of new KIR haplotypes and discusses the functional relevance of it.See accompanying article: http://dx.doi.org/10. 1002/eji.200425493 Introduction NK cells have developed strategies to detect and eliminate autologous cells displaying reduced expression of MHC class I molecules [1,2]. A sensitive and effective surveillance of MHC class I expression levels is an essential task of the natural immune system as it constitutes one of the weak spots of adaptive immunity: antigen-specific recognition of virally infected or malignantly transformed cells is generally mediated by CD8 T cells and, unfortunately, cytotoxic T cells are invariably dependent on presentation of those viral or tumor antigens in the context of MHC class I molecules. Thus T cells are in a way caged in the system of MHC restriction.It is thus not surprising that pathogens are constantly trying to escape the adaptive immune response by interfering with MHC class I expression. Viruses such as CMV and EBV, which have developed a largely commensal relationship with humans, have brought this strategy to perfection. They have in fact dedicated substantial parts of their precious genome to this task, which ranges from interference with antigen processing to blockade of HLA class I expression itself [3,4]. Similarly, down-regulation of MHC class I expression is a frequently observed phenomenon accompanying tumorigenesis [5,6]. Although a successful escape from adaptive immunity is obviously possible, there is reason to believe that most of these evasive maneuvers are counteracted by NK cells at an early stage.NK cells are functionally heterogeneous in their ability to recognize and eliminate target cells with . In contrast, stimulatory KIR have short cytoplasmic tails (indicated in the gene name by "S" for Short) lacking ITIM, but instead with a charged amino acid in the transmembrane region, which provides a docking site for the activating adapter molecule DAP12. There are only four KIR with clearly defined specificities, all of the inhibitory kind and all for HLA class I allotypes: KIR2DL2 as well as KIR2DL3 for HLA-C asn80 (i.e. HLA-C group 1), KIR2DL1 for HLA-C lys80 (i.e. HLA-C group 2), and KIR3DL1 for HLA-B (Bw4 epitope). Other inhibitory KIR have either less-well-defined sp...

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Recognition of HLA‐G by the NK cell receptor KIR2DL4 is not essential for human reproduction

Cited by 64 publications

References 51 publications

Domain Shuffling Has Been the Main Mechanism Forming New Hominoid Killer Cell Ig-Like Receptors

Domain Shuffling Has Been the Main Mechanism Forming New Hominoid Killer Cell Ig-Like Receptors

Molecular characterisation of KIR2DS2*005, a fusion gene associated with a shortened KIR haplotype

The KIR gene family: life in the fast lane of evolution

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