The mosaic of KIR haplotypes in rhesus macaques

Blokhuis, Jeroen H.; Wiel, Marit K. van der; Doxiadis, Gaby G. M.; Bontrop, Ronald E.

doi:10.1007/s00251-010-0434-3

Cited by 55 publications

(120 citation statements)

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“…2). However, based on our observations, no clearcut division between inhibitory or activating haplotypes, as observed in humans, exists in rhesus macaques, which is a confirmation of previous findings [36,37]. Indeed, if placentation is a strong selective force in humans [44], in rhesus macaques this influence may be less because the trophoblast-maternal interface is much smaller [45].…”

supporting

confidence: 86%

“…For the purpose of this particular study, whole blood was obtained during regular health checks. Peripheral blood mononuclear cells (PBMCs) were isolated from heparinized blood samples according to standard protocol [36]. Immortalized B cells were subsequently generated by culturing PBMCs after infection with herpes papiovirus, as previously described [21].…”

Section: Animals and Cellsmentioning

confidence: 99%

“…Subsequently, isolated vector was sequenced on an ABI 3130XL (Applied Biosystems, Foster City, CA, USA) with Pjet1.2 forward, Pjet1.2 reverse and one internal primer specific for Mamu-KIR: 5 0 -CGCAGGGACCTACAGATGTCG-3 0 . Sequences were obtained that phylogenetically cluster in previously described gene groups [36], with the exception of Mamu-KIR3DLW03, for which no sequences were retrieved. …”

mentioning

confidence: 99%

“…Genotypes can comprise three particular loci (Mamu-KIR3DL20, -KIR1D, and -KIR2DL04) with a centromeric location, and ten inhibitory KIR3DL and nine activating KIR3DS genes that map to the telomeric region, respectively. Segregation analysis of these KIR genotypes revealed at least 18 unique haplotypes [36]. The existing knowledge on haplotype data is based on a relatively small number of animals (n 5 9 [36], n 5 11 [37]), which displays, however, a complexity similar to that found in humans.…”

mentioning

confidence: 99%

“…This begs the question as to how much of the KIR system variability is actually present in rhesus macaques. Furthermore, a trend is apparent that no similar distinction of group A and B haplotypes, as observed in humans, can be made [36,37]. Therefore, to further investigate these questions, an extensive KIR gene content analysis has been performed on an outbred colony of rhesus macaques.…”

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confidence: 99%

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The extreme plasticity of killer cell Ig‐like receptor (KIR) haplotypes differentiates rhesus macaques from humans

et al. 2011

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NK cells are essential in shaping immune responses and play an important role during pregnancy and in controlling infections. Killer cell immunoglobulin-like receptors (KIRs) educate the NK cell and determine its state of activation. Our goal was to determine how the KIR repertoire of the rhesus macaque (Macaca mulatta) has been shaped during evolution. The presence or absence of 22 KIR gene groups was determined in 378 animals. Some unexpected observations were made in an outbred colony comprising animals of different origins. For instance, the KIR region appears to be highly plastic, and an unprecedented number of genotypes and haplotypes was observed. In contrast to humans, there is no distinction between group A and B haplotypes in the rhesus macaque, suggesting that different selective forces may be operative. Moreover, specific genes appear to be either present or absent in animals of different geographic origins. This extreme plasticity may have been propelled by co-evolution with the rhesus macaque MHC class I region, which shows signatures of expansion. The mosaic-like complexity of KIR genotypes as observed at the population level may represent an effective strategy for surviving epidemic infections. [3] but they are also involved with the vascularisation process during placentation, and thus contribute to reproductive success [4]. The education and activation state of the NK-cell is determined by the interactions of its receptors with their cognate ligands [5]. It is the shift in equilibrium of inhibitory and activating receptor signaling that ultimately leads to NK-cell activation in the form of cytokine production, cytotoxicity, or priming of the adaptive immune system [6].Killer cell immunoglobulin-like receptors (KIRs) may influence this balance through interactions with their ligands, the MHC molecules, which are called human leukocyte antigens 2719(HLA) in humans. Since both the HLA system and the KIR gene complex are characterized by variation in locus content, and segregate independent of each other, the potential array of interactions can vary considerably between individuals. Understanding the evolution and complexity of these receptor systems has broad medical relevance, since particular combinations of KIR and HLA alleles are associated with the outcome of viral infection, relapse of leukemia after transplantation, susceptibility to autoimmune disease, and successful pregnancy [7][8][9][10]. Because of its close evolutionary relationship to humans, and evidenced by similar immunological responses, the rhesus macaque (Macaca mulatta) is an important animal model to study the onset, progression, and outcome of infectious diseases, experimentally induced autoimmunity, and transplantation [11][12][13]. Moreover, certain human pathogens or their simiantrophic family members have adapted to primates as their natural host, and may show a host-specific pathology. Since in an experimental setting the onset of disease or the actual challenge with a pathogen can be controlled, it is possible to stu...

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supporting

confidence: 86%

Section: Animals and Cellsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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The extreme plasticity of killer cell Ig‐like receptor (KIR) haplotypes differentiates rhesus macaques from humans

et al. 2011

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Incorporation of Innate Immune Effector Mechanisms in the Formulation of a Vaccine Against HIV-1

Ansari

Mayne²,

Takahashi³

et al. 2011

Crossroads Between Innate and Adaptive Immunity III

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The realization of a major role for events that occur during acute viremia that dictate the course of disease both in HIV-1 infected humans and susceptible SIV infected non-human primates has prompted an intense interest in studies of the contribution of innate immune effector mechanisms. It is reasoned that findings from such studies may be important and need to be incorporated into the design and formulation of potential candidate vaccines against HIV-1. This review serves to outline the various non-human primate models that can best serve to address this issue, a summary of our knowledge on the various subsets of NK cells (one of the major innate immune cell lineage) that have an impact on the course of disease, the potential pathways that regulate their function and the potential role of the KIRs on SIV-induced disease course. Finally, the major points from this report and the data presented on similar subjects by other investigators is utilized to provide a summary of the potential future directions that we need to take in efforts to move this field forward.

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Characterization of rhesus macaque KIR genotypes and haplotypes

2010

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Certain combinations of the killer immunoglobulin-like receptors (KIR) and major histocompatibility complex class I ligands in humans predispose carriers to a variety of diseases, requiring sophisticated genotyping of the highly polymorphic and diverse KIR and HLA genes. Particularly, KIR genotyping is challenging due to polymorphisms (allelic substitutions), genomic diversity (presence/absence of genes), and frequent duplications. Rhesus macaques are often used as important animal models of human diseases such as, e.g. AIDS. However, typing of rhesus macaque KIR genes has not been described so far. In this study, we report the identification of additional novel rhesus macaque KIR cDNA sequences and a sequence-specific KIR genotyping assay. From a cohort of four rhesus macaque families with a total of 70 individuals, we identified 25 distinct KIR genotypes. Segregation analyses of KIR genes and of two polymorphic microsatellite markers allowed the identification of 21 distinct KIR haplotypes in these families, with five to 11 segregating KIR genes per haplotype. Our analyses confirmed and extended knowledge on differential gene KIR gene content in macaques and indicate that rhesus macaque and human KIR haplotypes show a comparable level of diversity and complexity.

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The mosaic of KIR haplotypes in rhesus macaques

Cited by 55 publications

References 47 publications

The extreme plasticity of killer cell Ig‐like receptor (KIR) haplotypes differentiates rhesus macaques from humans

The extreme plasticity of killer cell Ig‐like receptor (KIR) haplotypes differentiates rhesus macaques from humans

Incorporation of Innate Immune Effector Mechanisms in the Formulation of a Vaccine Against HIV-1

Characterization of rhesus macaque KIR genotypes and haplotypes

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