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

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Abstract

MIC molecules are stress-inducible ligands of the activating receptor NKG2D, which is expressed on natural killer cells and subsets of T lymphocytes. In rhesus macaques (Macaca mulatta), three different MIC sequences (MIC1, MIC2, MIC3) have been described that are closely related to but, according to phylogenetic analysis, do not represent orthologues of the human MICA and MICB genes. Although a single haplotype of the rhesus macaque Mhc (Mamu) has been completely sequenced, it remained unknown so far whether these three sequences are derived from two or three Mamu-MIC genes. We genotyped a cohort of 115 rhesus macaque individuals for the presence of MIC1, MIC2, and MIC3 sequences and analysed the segregation in families. All individuals were positive for MIC2, whereas only 66.1 and 80.9 % were positive for MIC1 and MIC3, respectively. MIC1 and MIC3 sequences segregated in offspring, indicating that they behave as alleles. Thus, we conclude that two MIC genes are present in the rhesus macaque Mhc, which we propose to designate as Mamu-MICA (MIC1 and MIC3) and Mamu-MICB (MIC2). “MIC1” and “MIC3” are regarded as divergent allelic lineages of the Mamu-MICA gene. Mamu-MIC genotyping of DNA of a cohort of 68 experimentally simian immunodeficiency virus (SIV)-infected rhesus macaques revealed no significant association of either of the two Mamu-MICA allelic lineages with differences in progression to AIDS-like symptoms.

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Acknowledgment

The authors are grateful for the expert technical assistance of Christiane Schwarz. R. D. and L. W. were supported by a grant from the Gesellschaft für AIDS-Forschung e. V. (Society for AIDS Research). V. M. is supported by the Research Training Group GRK 1034 financed by the Deutsche Forschungsgemeinschaft (German Research Council).

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Authors and Affiliations

  1. Department of Primate Genetics, German Primate Center, Kellnerweg 4, Göttingen, 37077, Germany

    Anne Averdam, Sandra Seelke, Immanuel Grützner, Cornelia Rosner, Christian Roos, Nico Westphal & Lutz Walter

  2. Department of Virology and Immunology, German Primate Center, Göttingen, Germany

    Christiane Stahl-Hennig & Ulrike Sauermann

  3. Primate Husbandry, German Primate Center, Göttingen, Germany

    Annette Schrod

  4. Department of Cellular and Molecular Immunology, University of Göttingen, Göttingen, Germany

    Vijayakumar Muppala & Ralf Dressel

Authors
  1. Anne Averdam
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  2. Sandra Seelke
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  3. Immanuel Grützner
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  4. Cornelia Rosner
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  5. Christian Roos
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  6. Nico Westphal
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  7. Christiane Stahl-Hennig
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  8. Vijayakumar Muppala
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  9. Annette Schrod
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  10. Ulrike Sauermann
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  11. Ralf Dressel
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  12. Lutz Walter
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Corresponding author

Correspondence to Lutz Walter.

Additional information

Anne Averdam and Sandra Seelke contributed equally.

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Fig. S1

Segregation analysis of MIC sequences in offspring. Mamu-MICB is represented by blue boxes, Mamu-MICA alleles in green (MIC1) and red (MIC3) boxes. Allelic differences are indicated by different color tones. Genotypes are based on PCR typing and sequencing of respective PCR products (PDF 46 kb)

Table 1

Genotyping of non-infected rhesus macaques (XLS 29 kb)

Table 2

Genotyping of SIV-infected rhesus macaques (XLS 20 kb)

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Averdam, A., Seelke, S., Grützner, I. et al. Genotyping and segregation analyses indicate the presence of only two functional MIC genes in rhesus macaques. Immunogenetics 59, 247–251 (2007). https://doi.org/10.1007/s00251-006-0187-1

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  • DOI: https://doi.org/10.1007/s00251-006-0187-1

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