Genotyping and segregation analyses indicate the presence of only two functional MIC genes in rhesus macaques

Averdam, Anne; Seelke, Sandra; Grützner, Immanuel; Rosner, Cornelia; Roos, Christian; Westphal, Nico; Stahl–Hennig∥, Christiane; Muppala, Vijayakumar; Schrod, Annette; Sauermann, Ulrike; Dressel, Ralf; Walter, Lutz

doi:10.1007/s00251-006-0187-1

Cited by 12 publications

(4 citation statements)

References 35 publications

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“…These microsatellites are localised within the MIC genes, which are situated next to the B region. As in the HLA system, each haplotype comprises two MIC genes (Averdam et al 2007; Doxiadis et al 2007b). In contrast to the situation in humans, however, rhesus macaques encode a MICB gene in conjunction with either a MICA or a MICAB gene, of which the latter is considered to be a fusion product of MICA and MICB (Doxiadis et al 2007b).…”

Section: Resultsmentioning

confidence: 99%

Haplotype diversity generated by ancient recombination-like events in the MHC of Indian rhesus macaques

et al. 2013

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The Mamu-A, Mamu-B, and Mamu-DRB genes of the rhesus macaque show several levels of complexity such as allelic heterogeneity (polymorphism), copy number variation, differential segregation of genes/alleles present on a haplotype (diversity) and transcription level differences. A combination of techniques was implemented to screen a large panel of pedigreed Indian rhesus macaques (1,384 individuals representing the offspring of 137 founding animals) for haplotype diversity in an efficient and inexpensive manner. This approach allowed the definition of 140 haplotypes that display a relatively low degree of region variation as reflected by the presence of only 17 A, 18 B and 22 DRB types, respectively, exhibiting a global linkage disequilibrium comparable to that in humans. This finding contrasts with the situation observed in rhesus macaques from other geographic origins and in cynomolgus monkeys from Indonesia. In these latter populations, nearly every haplotype appears to be characterised by a unique A, B and DRB region. In the Indian population, however, a reshuffling of existing segments generated “new” haplotypes. Since the recombination frequency within the core MHC of the Indian rhesus macaques is relatively low, the various haplotypes were most probably produced by recombination events that accumulated over a long evolutionary time span. This idea is in accord with the notion that Indian rhesus macaques experienced a severe reduction in population during the Pleistocene due to a bottleneck caused by geographic changes. Thus, recombination-like processes appear to be a way to expand a diminished genetic repertoire in an isolated and relatively small founder population.Electronic supplementary materialThe online version of this article (doi:10.1007/s00251-013-0707-8) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Haplotype diversity generated by ancient recombination-like events in the MHC of Indian rhesus macaques

et al. 2013

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“…In macaque species, two copies are present per haplotype, but there is heterogeneity . Each haplotype comprises a MICB gene segregating either with an MICA gene or a MICA/B hybrid . As is found in humans, the genes are polymorphic.…”

Section: Non‐classical Mhc Class I Molecules In Macaquesmentioning

confidence: 99%

Co‐evolution of the MHC class I and KIR gene families in rhesus macaques: ancestry and plasticity

Groot

Blokhuis

Otting

et al. 2015

Immunological Reviews

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SummaryResearchers dealing with the human leukocyte antigen (HLA) class I and killer immunoglobulin receptor (KIR) multi‐gene families in humans are often wary of the complex and seemingly different situation that is encountered regarding these gene families in Old World monkeys. For the sake of comparison, the well‐defined and thoroughly studied situation in humans has been taken as a reference. In macaques, both the major histocompatibility complex class I and KIR gene families are plastic entities that have experienced various rounds of expansion, contraction, and subsequent recombination processes. As a consequence, haplotypes in macaques display substantial diversity with regard to gene copy number variation. Additionally, for both multi‐gene families, differential levels of polymorphism (allelic variation), and expression are observed as well. A comparative genetic approach has allowed us to answer questions related to ancestry, to shed light on unique adaptations of the species’ immune system, and to provide insights into the genetic events and selective pressures that have shaped the range of these gene families.

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“…To induce MICA/B expression, the melanoma cells were cultured in Dulbecco’s modified Eagle’s medium (DMEM) with 10 μM of the histone deacetylase inhibitor suberoylanilide hydroxyamic acid (SAHA) (Qbiogene-Alexis, Grünberg, Germany) 20 hrs before being used for experiments [14]. Mouse L cells were co-transfected by electroporation with 30 μg of the cosmid A158 [15] containing the MICA gene of the rhesus macaque ( Macaca mulatta ) [16], and with 1 μg of the DsRed vector (Clontech, Heidelberg, Germany), which confers resistance to geneticin (G418, Invitrogen, Karlsruhe, Germany). After selection with geneticin (1 mg/ml), MICA expression was analysed in stable clones by flow cytometry.…”

Section: Methodsmentioning

confidence: 99%

The endogenous danger signals HSP70 and MICA cooperate in the activation of cytotoxic effector functions of NK cells

Elsner

Flügge

Lozano

et al. 2010

J Cellular Molecular Medi

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Although natural killer (NK) cells are often described as first line defence against infected or malignant cells which act without the need of prior activation, it is known now that the NK cell activity is tightly regulated by other cells and soluble factors. We show here that the stress-inducible heat shock protein (HSP) 70 activates human NK cells to kill target cells expressing major histocompatibility complex class I chain-related molecule A (MICA) in a natural killer group 2 member D (NKG2D-) dependent manner. The HSP70-derived peptide TKD (TKDNNLLGRFELSG) was able to replace the full-length HSP70 and to exert the same function. Interestingly, the expression of the cytotoxic effector protease granzyme B in NK cells was increased after TKD stimulation. When MICA and MICB expression was induced in human tumour cells by a histone deacetylase inhibitor and NK cells were activated by HSP70 or TKD, both treatments jointly improved the killing of the tumour cells. Thus, the synergistic activity of two stress-inducible immunological danger signals, HSP70 and MICA/B, leads to activation and enhanced cytotoxicity of human NK cells against tumour cells.

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Genotyping and segregation analyses indicate the presence of only two functional MIC genes in rhesus macaques

Cited by 12 publications

References 35 publications

Haplotype diversity generated by ancient recombination-like events in the MHC of Indian rhesus macaques

Haplotype diversity generated by ancient recombination-like events in the MHC of Indian rhesus macaques

Co‐evolution of the MHC class I and KIR gene families in rhesus macaques: ancestry and plasticity

The endogenous danger signals HSP70 and MICA cooperate in the activation of cytotoxic effector functions of NK cells

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