Abstract
Rhesus macaques are an animal model for the study of a variety of human diseases. The Chinese rhesus macaques have been widely used in biomedical research in recent years. However, the polymorphism of major histocompatibility complex (MHC) class I A region among different local populations of Chinese rhesus macaques has never been investigated. In this study, we identified 46 Mamu-A alleles by cDNA cloning and sequencing on a cohort of 53 Chinese rhesus monkeys including Zhiming, Chuanxi, and Fujian populations, of which 5 were first reported in rhesus monkeys. The frequencies of alleles were identified for each population. The result suggests that the repertoire of allelic variants of MHC class I A region found in different populations of Chinese macaques is largely non-overlapping. The frequencies of alleles and the popular allele are also different for different populations. PCR-SSP experiment further confirms the different frequencies of two alleles, Mamu-A*026:01 and Mamu-A*022:01, in additional 99 Zhiming monkeys and 191 Chuanxi monkeys. Our findings have important practical implications in that the origin of the individuals and the genetic polymorphism of the monkeys need to be considered at the level of local populations for Chinese rhesus monkeys in biomedical research. Further immunogenetic work is needed to investigate the MHC polymorphism among different populations of Chinese rhesus macaques and to reveal the functional implication of such polymorphism and disease outcome correlations.
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References
Allen TM, Sidney J, del Guercio MF, Glickman RL, Lensmeyer GL, Wiebe DA, DeMars R, Pauza CD, Johnson RP, Sette A, Watkins DI (1998) Characterization of the peptide binding motif of a rhesus MHC class I molecule (Mamu-A*01) that binds an immunodominant CTL epitope from simian immunodeficiency virus. J Immunol 160:6062–6071
Boyson JE, Shufflebotham C, Cadavid LF, Urvater JA, Knapp LA, Hughes AL, Watkins DI (1996) The MHC class I genes of the rhesus monkey: different evolutionary histories of MHC class I and II genes in primates. J Immunol 156:4656–4665
de Groot NG, Heijmans CMC, Koopman G, Verschoor EJ, Bogers WM, Bontrop RE (2011) TRIM5 allelic polymorphism in macaque species/populations of different geographic origins: its impact on SIV vaccine studies. Tissue Antigens 78:256–262
de Groot NG, Otting N, Robinson J, Blancher A, Lafont BAP, Marsh SGE, O’Connor DH, Shiina T, Walter L, Watkins DI, Bontrop RE (2012) Nomenclature report on the major histocompatibility complex genes and alleles of Great Ape, Old and New World monkey species. Immunogenetics 64(8):615–631
Doxiadis GGM, de Groot N, Otting N, Blokhuis JH, Bontrop RE (2011) Genomic plasticity of the MHC class I A region in rhesus macaques: extensive haplotype diversity at the population level as revealed by microsatellites. Immunogenetics 63:73–83
Fooden J (2000) Systematic review of the rhesus macaque, Macaca mulatta (Zimmermann, 1780). Field Museum of Natural History, Chicago
Gibbs RA, Rogers J, Katze MG, Bumgarner R, Weinstock GM, Mardis ER, Remington KA, Strausberg RL, Venter JC, Wilson RK, Batzer MA, Bustamante CD, Eichler EE, Hahn MW, Hardison RC, Makova KD, Miller W, Milosavljevic A, Palermo RE, Siepel A, Sikela JM, Attaway T, Bell S, Bernard KE, Buhay CJ, Chandrabose MN, Dao M, Davis C, Delehaunty KD, Ding Y et al (2007) Evolutionary and biomedical insights from the rhesus macaque genome. Science 316:222–234
Hayasaka K, Fujii K, Horai S (1996) Molecular phylogeny of macaques: implications of nucleotide sequences from an 896-base pair region of mitochondrial DNA. Mol Biol Evol 13:1044–1053
Jiang X, Wang Y, Ma S (1991) Taxonomic revision and distribution of subspecies of rhesus monkey (Macaca mulatta) in China. Zool Res 12:241–247
Joag SV, Stephens EB, Adams RJ, Foresman L, Narayan O (1994) Pathogenesis of SIVmac infection in Chinese and Indian rhesus macaques: effects of splenectomy on virus burden. Virology 200:436–446
Kaizu M, Borchardt GJ, Glidden CE, Fisk DL, Loffredo JT, Watkins DI, Rehrauer WM (2007) Molecular typing of major histocompatibility complex class I alleles in the Indian rhesus macaque which restrict SIV CD8+ T cell epitopes. Immunogenetics 59:693–703
Kanthaswamy S, Smith DG (2004) Effects of geographic origin on captive Macaca mulatta mitochondrial DNA variation. Comp Med 54:193–201
Kanthaswamy S, Satkoski J, George D, Kou A, Erickson BJ-A, Smith DG (2008) Hybridization and stratification of nuclear genetic variation in Macaca mulatta and M. fascicularis. Int J Primatol 29:1295–1311
Karl JA, Wiseman RW, Campbell KJ, Blasky AJ, Hughes AL, Ferguson B, Read DS, O’Connor DH (2008) Identification of MHC class I sequences in Chinese origin rhesus macaques. Immunogenetics 60:37–46
Kelley J, Walter L, Trowsdale J (2005) Comparative genomics of major histocompatibility complexes. Immunogenetics 56:683–695
Kiepiela P, Leslie AJ, Honeyborne I et al (2004) Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA. Nature 432:769–775
Kita YF, Hosomichi K, Kohara S, Itoh Y, Ogasawara K, Tsuchiya H, Torii R, Inoko H, Blancher A, Kulski JK, Shiina T (2009) MHC class I A loci polymorphism and diversity in three Southeast Asian populations of cynomolgus macaque. Immunogenetics 61:635–648
Knapp LA, Lehmann E, Piekarczyk MS, Urvater JA, Watkins DI (1997) A high frequency of Mamu-A*01 in the rhesus macaque detected by polymerase chain reaction with sequence-specific primers and direct sequencing. Tissue Antigens 50:657–661
Lim SY, Rogers T, Chan T et al (2010) TRIM5alpha modulates immunodeficiency virus control in rhesus monkeys. PLoS Pathog 6:e1000738
Ling B, Veazey RS, Luckay A, Penedo C, Xu K, Lifson JD, Marx PA (2002) SIV(mac) pathogenesis in rhesus macaques of Chinese and Indian origin compared with primary HIV infections in humans. AIDS 16:1489–1496
Loffredo JT, Bean AT, Beal DR et al (2008) Patterns of CD8+ immunodominance may influence the ability of Mamu-B*08-positive macaques to naturally control simian immunodeficiency virus SIVmac239 replication. J Virol 82:1723–1738
Ma X, Tang LH, Qu LB, Ma J, Chen L (2009) Identification of 17 novel major histocompatibility complex-A alleles in a population of Chinese origin rhesus macaques. Tissue Antigens 73:184–187
Martin MP, Qi Y, Gao X et al (2007) Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1. Nat Genet 39:733–740
Mothe BR, Sidney J, Dzuris JL, Liebl ME, Fuenger S, Watkins DI, Sette A (2002) Characterization of the peptide-binding specificity of Mamu-B*17 and identification of Mamu-B*17-restricted epitopes derived from simian immunodeficiency virus proteins. J Immunol 169(1):210–219
Naruse TK, Chen Z, Yanagida R, Yamashita T, Saito Y, Mori K, Akari H, Yasutomi Y, Miyazawa M, Matano T, Kimura A (2010) Diversity of MHC class I genes in Burmese-origin rhesus macaques. Immunogenetics 62:601–611
Otting N, Heijmans CM, Noort RC, de Groot NG, Doxiadis GG, van Rood JJ, Watkins DI, Bontrop RE (2005) Unparalleled complexity of the MHC class I region in rhesus macaques. Proc Natl Acad Sci USA 102:1626–1631
Otting N, de Vos-Rouweler AJ, Heijmans CM, de Groot NG, Doxiadis GG, Bontrop RE (2007) MHC class I A region diversity and polymorphism in macaque species. Immunogenetics 59:367–375
Otting N, Heijmans CM, van Wiel M, de Groot NG, Doxiadis G, Bontrop RE (2008) A snapshot of the Mamu-B genes and their allelic repertoire in rhesus macaques of Chinese origin. Immunogenetics 60:507–514
Ouyang D, Xu L, Dai Z, Shi H, Zhang G, Zheng Y, He X (2008) Identification of major histocompatibility complex class I alleles in Chinese rhesus macaques. Acta Biochim Biophys Sin (Shanghai) 40:919–927
Reimann KA, Parker RA, Seaman MS, Beaudry K, Beddall M, Peterson L, Williams KC, Veazey RS, Montefiori DC, Mascola JR, Nabel GJ, Letvin NL (2005) Pathogenicity of simian-human immunodeficiency virus SHIV-89.6P and SIVmac is attenuated in cynomolgus macaques and associated with early T-lymphocyte responses. J Virol 79:8878–8885
Robinson J, Waller MJ, Parham P, de Groot N, Bontrop R, Kennedy LJ, Stoehr P et al (2003) IMGT/HLA and IMGT/MHC: sequence databases for the study of the major histocompatibility complex. Nucleic Acids Res 31:311–314
Satkoski J, George D, Smith DG, Kanthaswamy S (2008) Genetic characterization of wild and captive rhesus macaques in China. J Med Primatol 37:67–80
Solomon C, Southwood S, Hoof I, Rudersdorf R, Peters B, Sidney J, Pinilla C, Garibaldi Marcondes MC, Ling BH, Marx P, Sette A, Mothé BR (2010) The most common Chinese rhesus macaque MHC class I molecule shares peptide binding repertoire with the HLA-B7 supertype. Immunogenetics 62:451–464
Southwood S, Solomon C, Hoof I, Rudersdorf R, Sidney J, Peters B, Wahl A, Hawkins O, Hildebrand W, Mothé BR, Sette A (2011) Functional analysis of frequently expressed Chinese rhesus macaque MHC class I molecules Mamu-A1*02601 and Mamu-B*08301 reveals HLA-A2 and HLA-A3 supertypic specificities. Immunogenetics 63:275–290
Tosi AJ, Morales JC, Melnick DJ (2002) Y-chromosome and mitochondrial markers in Macaca fascicularis indicate introgression with Indochinese M. mulatta and a biogeographic barrier in the Isthmus of Kra. Int J Primatol 23:161–178
Urvater JA, Otting N, Loehrke JH, Rudersdorf R, Slukvin II, Piekarczyk MS, Golos TG, Hughes AL, Bontrop RE, Watkins DI (2000) Mamu-I: a novel primate MHC class I B-related locus with unusually low variability. J Immunol 164:1386–1398
Vogel TU, Evans DT, Urvater JA, O’Connor DH, Hughes AL, Watkins DI (1999) Major histocompatibility complex class I genes in primates: co-evolution with pathogens. Immunol Rev 167:327–337
Welsh K, Bunce M (1999) Molecular typing for the MHC with PCR-SSP. Rev Immunogenet 1:157–176
Wiseman RW, Karl JA, Bimber BN, O’Leary CE, Lank SM, Tuscher JJ, Detmer AM, Bouffard P, Levenkova N, Turcotte CL, Szekeres E Jr, Wright C, Harkins T, O’Connor DH (2009) Major histocompatibility complex genotyping with massively parallel pyrosequencing. Nat Med 15:1322–1326
Yasutomi Y, McAdam SN, Boyson JE, Piekarczyk MS, Watkins DI, Letvin NL (1995) A MHC class I B locus allele-restricted simian immunodeficiency virus envelope CTL epitope in rhesus monkeys. J Immunol 154:2516–2522
Acknowledgments
The authors thank the anonymous reviewers for their helpful comments on this manuscript. The authors also thank IMGT Non-human Primate Nomenclature Committee for naming the Mamu-A sequences. This work was supported by the National Natural Science Foundation of China (grant nos. 30970416 and 31071987) and the National Facilities and Information Infrastructure for Science and Technology (grant no. 2005DKA21500).
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Li, A., Wang, X., Liu, Y. et al. Preliminary observations of MHC class I A region polymorphism in three populations of Chinese-origin rhesus macaques. Immunogenetics 64, 887–894 (2012). https://doi.org/10.1007/s00251-012-0645-x
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DOI: https://doi.org/10.1007/s00251-012-0645-x