Recognition of peptide–MHC class I complexes by activating killer immunoglobulin-like receptors

Stewart, Charles A.; Laugier-Anfossi, Fanny; Vély, Frederic; Saulquin, Xavier; Riedmuller, Jenifer; Tisserant, Agnès; Gauthier, Laurent; Romagné, François; Ferracci, Géraldine; Arosa, Fernando A.; Moretta, Alessandro; Sun, Peter D.; Ugolini, Sophie; Vivier, Éric

doi:10.1073/pnas.0503594102

Cited by 347 publications

(355 citation statements)

References 56 publications

(63 reference statements)

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“…However, as reported by Moesta et al [31], weak reactivity with HLA-C*1601 showed that KIR2DS2 has narrowed specificity for HLA-C, raising the possibility that it is also highly dependent on the peptide bound by HLA-C. Moesta et al were therefore unable to rule out the possibility that KIR2DS2 functions in the presence of peptides presented by HLA-C. In addition Stewart et al [32] suggest that some diseases may be associated with only certain combinations of KIR-HLA genes because the action of the activating KIR might be tissue specific due to specific peptide preferences. We therefore included KIR2DS2 in our analysis.…”

Section: Discussionmentioning

confidence: 55%

An increased frequency of NK cell receptor and HLA-C group 1 combinations in early-onset type 1 diabetes

Mehers

Long

Slik³

et al. 2011

Diabetologia

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Aims/hypothesis Natural killer (NK) cells serve as primary immune surveillance and are partially regulated by combinations of killer immunoglobulin-like receptor (KIR) genes and their HLA class I ligands. Alterations in NK cell activity have been associated with type 1 diabetes. The aim of this study was to determine whether KIR-HLA class I gene frequency: (1) is altered in a current population with type 1 diabetes compared with healthy controls; and (2) has changed over the half century in which the incidence of type 1 diabetes has increased rapidly.Methods KIR-HLA class I gene frequencies were compared in 551 individuals diagnosed with type 1 diabetes ≤15 years of age (394 in a current cohort and 157 from the historical 'Golden Years' cohort) and 168 healthy controls. The overall balance of activation and inhibition was analysed using KIR-HLA genotype models. Results Children with type 1 diabetes who were positive for KIR2DS2/KIR2DL2 and KIR2DL3 were more often homozygous for HLA-C group 1 and this effect was strongest in children diagnosed with diabetes before the age of 5 years (p=0.003, corrected p [p corr ]=0.012) and (p=0.001, p corr = 0.004), respectively. Children with type 1 diabetes have fewer inhibitory KIRs with their corresponding ligands compared with healthy controls (p=1.9×10 −4 ). This pattern of NK activation has not changed significantly in individuals with type 1 diabetes over the last half century. Conclusions/interpretation Activating combinations of KIR-HLA genes are more frequent in young children with type 1 diabetes diagnosed in the first 5 years of life, suggesting that NK cell responses may be altered in this group.

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Section: Discussionmentioning

confidence: 55%

An increased frequency of NK cell receptor and HLA-C group 1 combinations in early-onset type 1 diabetes

Mehers

Long

Slik³

et al. 2011

Diabetologia

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“…Overlapping specificity of activating and inhibitory pairs is a common theme for several MHC-binding NK receptors including Ly49, KIR, and CD94/NKG2 [28][29][30][31]. The basis for the development of parallel inhibitory and activating NKR-P1 recognition systems for the same ligands is not clear, but the existence of viral Clr decoys [23] suggests that it may be pathogen-driven.…”

Section: Discussionmentioning

confidence: 99%

Two major groups of rat NKR‐P1 receptors can be distinguished based on chromosomal localization, phylogenetic analysis and Clr ligand binding

et al. 2009

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A major subset of non-alloreactive NK cells in PVG strain rats is generally low in Ly49 receptors, but expresses the rat NKR-P1B PVG receptor (previously termed NKR-P1C). The NKR-P1B 1 NK subset is inhibited by a non-polymorphic target cell ligand, which we have shown here to be a C-type lectin-related molecule (Clr). Clr11 ligates two divergent NKR-P1B alleles as judged by an NFAT-driven reporter assay, and inhibits NK-cell cytotoxicity of NKR-P1B 1 NK cells. Clr11 also interacts with the prototypic NKR-P1A receptor and exerts a stimulatory influence on NK lysis. NKR-P1A and B are encoded by adjacent genes in the proximal part of the NK gene complex and show close sequence homology in their extracellular region. They diverge from another pair, NKR-P1F and -G, which is encoded by a second, distal Nkrp1 gene cluster. NKR-P1F and -G bind an overlapping panel of Clr ligands, but not Clr11. Rat Clr molecules appear to be constitutively expressed by hematopoietic cells; expression in tumor cell lines is more variable. The data show the existence of two phylogenetic groups of NKR-P1 molecules, which demonstrate conservation of ligand-binding properties independent of signaling function.Key words: Cytotoxicity . NK cells . Receptor . Rodent Introduction NK cells express several families of killer cell lectin-like receptors (KLR). These are type II transmembrane proteins encoded by the NK gene complex (NKC), which is located on chromosome 4 in the rat [1,2]. The NKR-P1 molecules (KLRB or CD161) were among the first KLR to be characterized, but their function long remained elusive [3][4][5]. Although the NKR-P1 family has expanded to include both activating and inhibitory members in rodents, it consists of only one member in several other mammalian species, including in human [6]. The nature of their ligands has been controversial [7,8], but it has recently been shown that members of another KLR-related receptor family, the C-type lectin-related (Clr) molecules [9], also termed C-type lectin 2D (CLEC2D), can act as ligands for certain NKR-P1 molecules [10,11]. The Clr gene family also shows considerable expansion in rodents and the Clr genes are interspersed with the Nkrp1 genes in the proximal (centromeric) part of the NKC. A recent analysis concluded that there are 11 Clr/Clec2d genes in the rat BN strain genome, which were numbered consecutively from proximal to distal. One of these (Clr8) is most likely only a gene fragment, which could have been excluded, but we will nevertheless adhere to the Clr numbering suggested by Hao et al. [6].In the mouse, the inhibitory NKR-P1B and -D receptors both bind Clrb (also termed Ocil). Clrb is constitutively expressed by hematopoietic cells and inhibits cytolytic activity of NKR-P1B/ D-expressing NK cells [10,11]. The activating NKR-P1F receptor has been shown to bind another Clr molecule, Clrg, by the use of a reporter assay and soluble recombinant proteins [11] functional consequence of this interaction remains obscure. In human, the NKR-P1A receptor binds a Clr orthologue term...

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“…14 A number of activatory KIR (2DS1, 2DS2) also bind to HLA class I, albeit with weaker affinity and variation in the presence or absence of each can influence NK cell function. 15,16 Several studies indicate that KIRs have evolved in humans to fulfill diverse functions as a consequence of a wide range of evolutionary pressures. The opposing functions of activatory and inhibitory KIR is believed to reflect underlying processes of balancing and positive selection in response to pressures imposed by pathogens and coevolution with their rapidly evolving HLA class I ligands.…”

Section: Introductionmentioning

confidence: 99%

Receptor systems controlling natural killer cell function are genetically stratified in Europe

et al. 2009

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Natural killer (NK) cells are components of the innate immune system that function in identifying and destroying aberrant or pathogen-infected cells. These functions are largely controlled by killer cell immunoglobulin-like receptors (KIRs). KIRs inhibit and activate NK cell functions through interactions with their ligands, epitopes encoded by human leukocyte antigen (HLA) class I genes (HLA-C1, C2 and Bw4). Genes that encode KIR and their HLA ligands vary in frequency across human populations. Here, we characterize two Irish populations for KIR and HLA and determine the spatial distribution of functionally important KIR:HLA systems in Europe, a region known for its considerable underlying genetic stratification. We find that Southern Europe is a region characterized by higher frequencies of activatory KIR and strong inhibitory HLA ligand systems (2DL1:HLA-C2 and 3DL1:Bw4). A lower frequency of activatory KIR and the predominance of a comparatively weaker inhibitory ligand system (2DL3:HLA-C1) are observed northwards. Despite contrasting KIR:HLA systems in Northern and Southern Europe, there is a clear balance between inhibitory and activatory repertoires, and their ligands in both regions. These findings show 'functional stratification' of the epistatic KIR:HLA receptor system in Europe, the presence of which will likely affect NK cell-mediated immunity across different populations.

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Recognition of peptide–MHC class I complexes by activating killer immunoglobulin-like receptors

Cited by 347 publications

References 56 publications

An increased frequency of NK cell receptor and HLA-C group 1 combinations in early-onset type 1 diabetes

An increased frequency of NK cell receptor and HLA-C group 1 combinations in early-onset type 1 diabetes

Two major groups of rat NKR‐P1 receptors can be distinguished based on chromosomal localization, phylogenetic analysis and Clr ligand binding

Receptor systems controlling natural killer cell function are genetically stratified in Europe

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