Characterization of full-length MHC class II sequences in Indonesian and Vietnamese cynomolgus macaques.

Wisconsin National Primate Research Center, University of Wisconsin-Madison, USA.
Immunogenetics (Impact Factor: 2.49). 05/2011; 63(9):611-8. DOI: 10.1007/s00251-011-0537-5
Source: PubMed

ABSTRACT In recent years, the use of cynomolgus macaques in biomedical research has increased greatly. However, with the exception of the Mauritian population, knowledge of the MHC class II genetics of the species remains limited. Here, using cDNA cloning and Sanger sequencing, we identified 127 full-length MHC class II alleles in a group of 12 Indonesian and 12 Vietnamese cynomolgus macaques. Forty two of these were completely novel to cynomolgus macaques while 61 extended the sequence of previously identified alleles from partial to full length. This more than doubles the number of full-length cynomolgus macaque MHC class II alleles available in GenBank, significantly expanding the allele library for the species and laying the groundwork for future evolutionary and functional studies.


Available from: Ericka A Becker, May 16, 2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pig-tailed macaques (Macaca nemestrina) serve as important models for human infectious disease research. Major histocompatibility complex (MHC) class II molecules are important to this research since they present peptides to CD4+ T cells. Despite the importance of characterizing the MHC-II alleles expressed in model species like pig-tailed macaques, to date, less than 150 MHC-II alleles have been named for the six most common classical class II loci (DRA, DRB, DQA, DQB, DPA, and DPB) in this population. Additionally, only a small percentage of these alleles are full-length, making it impossible to use the known sequence for reagent development. To address this, we developed a fast, high-throughput method to discover full-length MHC-II alleles and used it to characterize alleles in 32 pig-tailed macaques. By this method, we identified 128 total alleles across all six loci. We also performed an exon 2-based genotyping assay to validate the full-length sequencing results; this genotyping assay could be optimized for use in determining MHC-II allele frequencies in large cohorts of pig-tailed macaques.
    Immunogenetics 08/2014; 66(11). DOI:10.1007/s00251-014-0797-y · 2.49 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Rhesus macaques have long been used as animal models for various human diseases; the susceptibility and/or resistance to some of these diseases are related to the major histocompatibility complex (MHC). To gain insight into the MHC background and to facilitate the experimental use of Chinese rhesus macaques, Mamu-DPA1, Mamu-DQA1, and Mamu-DRA alleles were investigated in 30 Chinese rhesus macaques by gene cloning and sequencing. A total of 14 Mamu-DPA1, 17 Mamu-DQA1, and 9 Mamu-DRA alleles were identified in this study. Of these alleles, 22 novel sequences have not been documented in earlier studies, including nine Mamu-DPA1, ten Mamu-DQA1, and three Mamu-DRA alleles. Interestingly, like Mafa-DQA1 and Mafa-DPA1, more than two Mamu-DQA1 and Mamu-DPA1 alleles were detected in one animal in this study, which suggested that they might represent gene duplication. If our findings can be validated by other studies, it will further increase the number of known Mamu-DPA1 and Mamu-DQA1 polymorphisms. Our data also indicated significant differences in MHC class II allele distribution among the Chinese rhesus macaques, Vietnamese cynomolgus macaques, and the previously reported rhesus macaques, which were mostly of Indian origin. This information will not only promote the understanding of Chinese rhesus macaque MHC diversity and polymorphism but will also facilitate the use of Chinese rhesus macaques in studies of human disease.
    Immunogenetics 09/2013; DOI:10.1007/s00251-013-0736-3 · 2.49 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The cynomolgus macaque (Macaca fascicularis) is currently used as an animal model in various fields of immunology especially in the development of innovative vaccines for the prevention and treatment of infectious diseases. The polymorphism of the major histocompatibility complex (MHC) influences the development of adaptive immune responses and it is crucial to characterize the polymorphism of cynomolgus MHC genes. We present here a systematic study of the MHC class II haplotypes in the Filipino macaque population. By the study of a large sample of Filipino animals (N = 353), we have characterized 18 MHC class II haplotypes by means of genotyping seven microsatellites. The animals were DRB genotyped by means of PCR-SSO or DGGE-sequencing on genomic amplified fragments. We cloned and sequenced the complementary DNA (cDNA) of DQA, DQB, DPA, and DPB genes of 117 animals. Combining the microsatellite genotyping and cDNA characterized in the 117 animals, we defined genetic association between the cDNA and the microsatellites and characterized 18 MHC class II haplotypes. For 104 animals out of the 353 studied, the presence of a recombinant haplotype was highly probable. Thirty-four percent of recombination was located in 256 kb segment between D6S2876 and D6S2747 microsatellites, a region encompassing several hot spots of recombination in the human MHC.
    Immunogenetics 02/2014; DOI:10.1007/s00251-014-0764-7 · 2.49 Impact Factor