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High diversity of MIC genes in non-human primates

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Abstract

The human MHC class I (MHC-I) chain-related genes A and B (MICA and MICB) encode stress-induced glycoproteins, ligands for the activating receptor NKG2D. They display an unusually high degree of polymorphism, next only to that of classical MHC-I. The functional relevance and selective pressure behind this peculiar polymorphism, which is quite distinct from that of classical MHC-I, remain largely unknown. This study increases the repertoire of allelic sequences determined for the MIC genes of non-human primates. Sequencing (mainly exons 2, 3, 4, 5) MIC genes of 72 Macaca fascicularis (Mafa), 63 Pan troglodytes (Patr), and 18 Gorilla gorilla (Gogo) individuals led to the identification of 35, 14, and 3 new alleles, respectively. Additionally, we confirm the existence of three independent MIC genes in M. fascicularis, i.e., Mafa-MICA, Mafa-MICB, and Mafa-MICB/A, the latter being a hybrid of Mafa-MICB and Mafa-MICA. By multiple sequence alignment and phylogenetic analysis, we further demonstrate that the present day MIC genes most likely derive from a single human MICB-like ancestral gene.

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Acknowledgments

We wish to thank Dr. Alejandro P. Rooney for the primate samples. This work is published under the framework of the LABEX TRANSPLANEX [ANR-11-LABX-0070_TRANSPLANTEX] which benefits from the funding of the French government, funds managed by the French National Research Agency (ANR) as part of the “Investments for the future” program. Additional support was provided by Genomax, the Strasbourg School of Medicine Next Generation Sequencing center, the French Ministry of Research, and the Institut Universitaire de France (IUF).

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Authors and Affiliations

  1. Laboratoire d’ImmunoRhumatologie Moléculaire, INSERM UMR_S1109, Plateforme GENOMAX, LabEx Transplantex, Centre de Recherche d’Immunologie et d’Hématologie. Faculté de Médecine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, 4 Rue Kirschleger, 67085, Strasbourg, France

    Alice Meyer, Raphael Carapito, Louise Ott, Mirjana Radosavljevic, Philippe Georgel & Seiamak Bahram

  2. Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA

    Erin J. Adams

  3. Departments of Structural Biology and Microbiology & Immunology, Stanford University, Stanford, CA, 94305, USA

    Peter Parham

  4. Department of Comparative Genetics, Biomedical Primate Research Center, Rijswijk, The Netherlands

    Ronald E. Bontrop

  5. Laboratoire d’immunogénétique Moléculaire EA3034, Université Paul Sabatier, Toulouse, France

    Antoine Blancher

  6. Laboratoire d’immunologie, CHU de Toulouse, Hôpital de Rangueil, Toulouse, France

    Antoine Blancher

Authors
  1. Alice Meyer
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  2. Raphael Carapito
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  3. Louise Ott
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  4. Mirjana Radosavljevic
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  5. Philippe Georgel
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  6. Erin J. Adams
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  7. Peter Parham
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  8. Ronald E. Bontrop
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  9. Antoine Blancher
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  10. Seiamak Bahram
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Corresponding author

Correspondence to Seiamak Bahram.

Additional information

Alice Meyer and Raphael Carapito contributed equally to this work.

Electric supplementary materials

Supplementary Table 1

GenBank accession numbers of Mafa, Patr and Gogo MIC genes (JPEG 1.21 MB).

Supplementary Figure 1

Multiple alignment of exon 5 of human MICB and Mafa-MICBThe human MICA reference sequence (Hu-MICA*001; GenBank accession number X92841) is used as reference. GCT triplets are underlined (DOCX 25.4 kb).

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Meyer, A., Carapito, R., Ott, L. et al. High diversity of MIC genes in non-human primates. Immunogenetics 66, 581–587 (2014). https://doi.org/10.1007/s00251-014-0791-4

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