Rhesus Macaque Inhibitory and Activating KIR3D Interact with Mamu-A–Encoded Ligands

Rosner, Cornelia; Kruse, Philip H.; Hermes, Meike; Otto, N.; Walter, Lutz

doi:10.4049/jimmunol.1002634

Cited by 33 publications

(65 citation statements)

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“…The functional implications of candidate KIR genes can already be investigated. Recently, it was reported that Mamu-KIR3DLW03, KIR3DL05, and possibly KIR3DS05 gene products can interact with Mamu-A1 Ã 001:01 and -A3 Ã 13:11 molecules [50]. Notably, these first two inhibitory genes are enriched in our animals of Chinese origin while the latter activating one is absent (Fig.…”

Section: Discussionmentioning

confidence: 78%

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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Section: Discussionmentioning

confidence: 78%

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

et al. 2011

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“…It is evident in primates that different lineages of KIR genes have been expanded concomitantly with species‐specific evolution of MHC class I genes 216. In rhesus macaque, an important animal model of human diseases such as AIDS, binding of certain KIR is influenced by the same MHC epitopes (Bw4 and Bw6) that are important determinants of human KIR interactions 217. In the last decade, progress has been made in characterizing KIR genes in primates and developing specific genotyping assays 218, 219.…”

Section: Kir Model Systemsmentioning

confidence: 99%

Deciphering the killer‐cell immunoglobulin‐like receptor system at super‐resolution for natural killer and T‐cell biology

et al. 2016

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SummaryKiller‐cell immunoglobulin‐like receptors (KIRs) are components of two fundamental biological systems essential for human health and survival. First, they contribute to host immune responses, both innate and adaptive, through their expression by natural killer cells and T cells. Second, KIR play a key role in regulating placentation, and hence reproductive success. Analogous to the diversity of their human leucocyte antigen class I ligands, KIR are extremely polymorphic. In this review, we describe recent developments, fuelled by methodological advances, that are helping to decipher the KIR system in terms of haplotypes, polymorphisms, expression patterns and their ligand interactions. These developments are delivering deeper insight into the relevance of KIR in immune system function, evolution and disease.

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“…Several candidate MHC-KIR interactions have been reported for rhesus macaques based on in vitro binding assays (Rosner et al 2011). Colantonio and colleagues made the serendipitous discovery that a recombinant soluble MHC tetramer folded around certain SIV-derived peptides could bind to the surface of lymphocytes from a subset of uninfected animals with no prior exposure to SIV or SIV antigens (Colantonio et al 2011).…”

Section: The Mhc Locus In Primate Modelsmentioning

confidence: 99%

Host Genes Important to HIV Replication and Evolution

Telenti

Johnson²

2012

Cold Spring Harbor Perspectives in Medicine

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Rhesus Macaque Inhibitory and Activating KIR3D Interact with Mamu-A–Encoded Ligands

Cited by 33 publications

References 50 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

Deciphering the killer‐cell immunoglobulin‐like receptor system at super‐resolution for natural killer and T‐cell biology

Host Genes Important to HIV Replication and Evolution

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