The Structure of the Atypical Killer Cell Immunoglobulin-like Receptor, KIR2DL4

Moradi, Shoeib; Berry, Richard; Pymm, Phillip; Hitchen, Corinne R; Beckham, Simone A.; Wilce, Matthew C. J.; Walpole, Nicholas George; Clements, Craig Steven; Reid, Hugh H.; Perugini, Matthew A.; Brööks, Andrëw G.; Rossjohn, Jamie; Vivian, J.P.

doi:10.1074/jbc.m114.612291

Cited by 37 publications

(44 citation statements)

References 57 publications

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“…The sixth gene, KIR2DL4 , is expressed on mRNA level in every NK cell but is weakly expressed, if at all, on the cell surface of CD56 dim NK cells . Although originally described as HLA‐G‐specific receptor, recent evidence argues against direct interaction of HLA‐G with KIR2DL4 . Due to the fact that KIR expression in A/A haplotype donors can be fully discriminated by flow cytometry ( Table ), most of the information we presently have about the phenotype and the factors that shape human NK cell repertoires is based on the analysis of donors that are homozygous for group A haplotypes .…”

Section: Composition Of Human Nk Cell Repertoiresmentioning

confidence: 99%

Human KIR repertoires: shaped by genetic diversity and evolution

Manser

Weinhold

Uhrberg

2015

Immunological Reviews

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Killer cell immunoglobulin-like receptors (KIRs) on natural killer (NK) cells are crucially involved in the control of cancer development and virus infection by probing cells for proper expression of HLA class I. The clonally distributed expression of KIRs leads to great combinatorial diversity that develops in the presence of the evolutionary older CD94/NKG2A receptor to create highly stochastic but tolerant repertoires of NK cells. These repertoires are present at birth and are subsequently shaped by an individuals' immunological history toward recognition of self. The single most important factor that shapes functional NK cell repertoires is the genetic diversity of KIR, which is characterized by the presence of group A and B haplotypes with complementary gene content that are present in all human populations. Group A haplotypes constitute the minimal genetic entity that provides high affinity recognition of all major human leukocyte antigen class I-encoded ligands, whereas group B haplotypes contribute to the diversification of NK cell repertoires by providing sets of stimulatory KIR genes that modify NK cell responses. We suggest a cooperative model for the balancing selection of A and B haplotypes, which is driven by the need to provide a suitable corridor of repertoire complexity in which A/A individuals with only 16 different KIR combinations coexist with A/B and B/B donors expressing up to 2048 different clone types.

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Section: Composition Of Human Nk Cell Repertoiresmentioning

confidence: 99%

Human KIR repertoires: shaped by genetic diversity and evolution

Manser

Weinhold

Uhrberg

2015

Immunological Reviews

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“…The structures of seven KIRs (2DL1, 2DL2, 2DS2, 2DL3, 2DL4, 2DS4, and 3DL1) have been determined either in isolation or in complex with a HLA class I protein ( Fig. A–F ).…”

Section: Common Features Of Kir‐hla Interactionsmentioning

confidence: 99%

“…Understanding ligand recognition and signal transduction by KIR2DL4 is further complicated by its largely endosomal localization, a property dependent on its ectodomains . The resolution of the structure of KIR2DL4 showed that like other KIR2D receptors, the D0‐D2 domains of KIR2DL4 adopted a ‘V’ architecture, yet with a less acute hinge angle of approximately 85° relative to that between the D1 and D2 domains in other KIR . Most notably however, unlike other KIR receptors, which exist as monomers in solution, KIR2DL4 was observed as a tetramer ( Fig.…”

Section: D0‐d2 Kir: More Questions Than Answersmentioning

confidence: 99%

A bird's eye view of NK cell receptor interactions with their MHC class I ligands

Saunders

Vivian

O’Connor

et al. 2015

Immunological Reviews

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“…Such isoforms may act instead of KIR2DL4, which emerged in this study not associated with susceptibility to miscarriage or protection against disease in female patients. Moreover, the studies on the crystal structure of KIR2DL4 showed that this receptor oligomerizes to tetramers possibly because of the absence of D0 domain glycosylation (Moradi et al 2015). This was supposed to preclude an interaction of receptor with HLA.…”

Section: Discussionmentioning

confidence: 99%

“…This was supposed to preclude an interaction of receptor with HLA. Indeed, Moradi et al (2015) were unable to detect an interaction between KIR2DL4 and a panel of 100 pHLA-Ia or HLA-G by single HLA-antigen bead assay and by surface plasmon resonance. Therefore, a self-association of KIR2DL4 could regulate ligand binding and subsequent signal transduction.…”

Section: Discussionmentioning

confidence: 99%

Possible Role of HLA-G, LILRB1 and KIR2DL4 Gene Polymorphisms in Spontaneous Miscarriage

Nowak

Malinowski

Barcz

et al. 2016

Arch. Immunol. Ther. Exp.

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The KIR2DL4 receptor and its ligand HLA-G are considered important for fetal-maternal immune tolerance and successful pregnancy. The absence of a particular variant of KIR2DL4 might be a bad prognostic factor for pregnancy outcome. However, it could be compensated by the presence of the respective LILRB1 allele. Therefore, we investigated the KIR2DL4, LILRB1 and HLA-G polymorphisms in 277 couples with spontaneous abortion and 219 control couples by HRM, PCR-SSP and RFLP methods. We found a protective effect of women’s heterozygosity in −716 HLA-G (p = 0.0206) and LILRB1 (p = 0.0131) against spontaneous abortion. Surprisingly, we observed more 9A/10A genotypes of KIR2DL4 gene carriers in the group of male partners from the miscarriage group in comparison to the men from the control group (p = 0.0288). Furthermore, there was no association of women’s KIR2DL4 polymorphism with susceptibility to spontaneous abortion. Multivariate analysis indicated that women’s −716 HLA-G and LILRB1 and men’s KIR2DL4 9A/10A are important in terms of the protection or susceptibility to miscarriage, respectively (p = 0.00968). In conclusion, a woman’s heterozygosity in HLA-G and LILRB1 might be an advantage for a success of reproduction, but the partner’s heterozygosity in 9A/10A KIR2DL4 alleles might not.Electronic supplementary materialThe online version of this article (doi:10.1007/s00005-016-0389-7) contains supplementary material, which is available to authorized users.

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The Structure of the Atypical Killer Cell Immunoglobulin-like Receptor, KIR2DL4

Cited by 37 publications

References 57 publications

Human KIR repertoires: shaped by genetic diversity and evolution

Human KIR repertoires: shaped by genetic diversity and evolution

A bird's eye view of NK cell receptor interactions with their MHC class I ligands

Possible Role of HLA-G, LILRB1 and KIR2DL4 Gene Polymorphisms in Spontaneous Miscarriage

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