Comprehensive characterization of MHC class II haplotypes in Mauritian cynomolgus macaques
- 401 Downloads
There are currently no nonhuman primate models with fully defined major histocompatibility complex (MHC) class II genetics. We recently showed that six common MHC haplotypes account for essentially all MHC diversity in cynomolgus macaques (Macaca fascicularis) from the island of Mauritius. In this study, we employ complementary DNA cloning and sequencing to comprehensively characterize full length MHC class II alleles expressed at the Mafa-DPA, -DPB, -DQA, -DQB, -DRA, and -DRB loci on the six common haplotypes. We describe 34 full-length MHC class II alleles, 12 of which are completely novel. Polymorphism was evident at all six loci including DPA, a locus thought to be monomorphic in rhesus macaques. Similar to other Old World monkeys, Mauritian cynomolgus macaques (MCM) share MHC class II allelic lineages with humans at the DQ and DR loci, but not at the DP loci. Additionally, we identified extensive sharing of MHC class II alleles between MCM and other nonhuman primates. The characterization of these full-length-expressed MHC class II alleles will enable researchers to generate MHC class II transferent cell lines, tetramers, and other molecular reagents that can be used to explore CD4+ T lymphocyte responses in MCM.
KeywordsMHC Immunogenetics Macaca fascicularis
This work was supported by NIAID contract number HHSN266200400088C/N01-AI-40088 and 1 R24 RR021745-01A1. This publication was made possible in part by grant number P51 RR000167 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), to the Wisconsin National Primate Research Center, University of Wisconsin—Madison. This publication was also made possible in part by grant number GM43940 from the NIH to A.L.H. This research was conducted in part at a facility constructed with support from Research Facilities Improvement Program grant numbers RR15459-01 and RR020141-01. This publication’s contents are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH.
We thank Jason Wojcechowskyj for helping design PCR primers for MHC class II alleles. We thank Nel Otting, Natasja de Groot, and the IMGT for assigning uniform allele nomenclature. We thank Ronald Bontrop, Robert DeMars, and other members of the O’Connor lab for helpful discussions.
- Allen TM, Mothe BR, Sidney J, Jing P, Dzuris JL, Liebl ME, Vogel TU, O’Connor DH, Wang X, Wussow MC, Thomson JA, Altman JD, Watkins DI, Sette A (2001) CD8(+) lymphocytes from simian immunodeficiency virus-infected rhesus macaques recognize 14 different epitopes bound by the major histocompatibility complex class I molecule mamu-A*01: implications for vaccine design and testing. J Virol 75:738–749PubMedCrossRefGoogle Scholar
- 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 160:6062–6071PubMedGoogle Scholar
- Allen TM, Vogel TU, Fuller DH, Mothe BR, Steffen S, Boyson JE, Shipley T, Fuller J, Hanke T, Sette A, Altman JD, Moss B, McMichael AJ, Watkins DI (2000) Induction of AIDS virus-specific CTL activity in fresh, unstimulated peripheral blood lymphocytes from rhesus macaques vaccinated with a DNA prime/modified vaccinia virus Ankara boost regimen. J Immunol 164:4968–4978PubMedGoogle Scholar
- DeMars R, Chang CC, Shaw S, Reitnauer PJ, Sondel PM (1984) Homozygous deletions that simultaneously eliminate expressions of class I and class II antigens of EBV-transformed B-lymphoblastoid cells. I. Reduced proliferative responses of autologous and allogeneic T cells to mutant cells that have decreased expression of class II antigens. Hum Immunol 11:77–97PubMedCrossRefGoogle Scholar
- Kaufmann DE, Bailey PM, Sidney J, Wagner B, Norris PJ, Johnston MN, Cosimi LA, Addo MM, Lichterfeld M, Altfeld M, Frahm N, Brander C, Sette A, Walker BD, Rosenberg ES (2004) Comprehensive analysis of human immunodeficiency virus type 1-specific CD4 responses reveals marked immunodominance of gag and nef and the presence of broadly recognized peptides. J Virol 78:4463–4477PubMedCrossRefGoogle Scholar
- Kuroda MJ, Schmitz JE, Lekutis C, Nickerson CE, Lifton MA, Franchini G, Harouse JM, Cheng-Mayer C, Letvin NL (2000) Human immunodeficiency virus type 1 envelope epitope-specific CD4(+) T lymphocytes in simian/human immunodeficiency virus-infected and vaccinated rhesus monkeys detected using a peptide-major histocompatibility complex class II tetramer. J Virol 74:8751–8756PubMedCrossRefGoogle Scholar
- Kuroda MJ, Schmitz JE, Barouch DH, Craiu A, Allen TM, Sette A, Watkins DI, Forman MA, Letvin NL (1998) Analysis of Gag-specific cytotoxic T lymphocytes in simian immunodeficiency virus-infected rhesus monkeys by cell staining with a tetrameric major histocompatibility complex class I–peptide complex. J Exp Med 187:1373–1381PubMedCrossRefGoogle Scholar
- Lawler JV, Endy TP, Hensley LE, Garrison A, Fritz EA, Lesar M, Baric RS, Kulesh DA, Norwood DA, Wasieloski LP, Ulrich MP, Slezak TR, Vitalis E, Huggins JW, Jahrling PB, Paragas J (2006) Cynomolgus macaque as an animal model for severe acute respiratory syndrome. PLoS Med 3:677–686CrossRefGoogle Scholar
- Loffredo JT, Rakasz EG, Giraldo JP, Spencer SP, Grafton KK, Martin SR, Napoe G, Yant LJ, Wilson NA, Watkins DI (2005) Tat(28–35)SL8-specific CD8+ T lymphocytes are more effective than Gag(181–189)CM9-specific CD8+ T lymphocytes at suppressing simian immunodeficiency virus replication in a functional in vitro assay. J Virol 79:14986–14991PubMedCrossRefGoogle Scholar
- Mills KH, Barnard AL, Williams M, Page M, Ling C, Stott EJ, Silvera P, Taffs F, Kingsman AS, Adams SE et al (1991) Vaccine-induced CD4+ T cells against the simian immunodeficiency virus gag protein. Epitope specificity and relevance to protective immunity. J Immunol 147:3560–3567PubMedGoogle Scholar
- O’Connor DH, Mothe BR, Weinfurter JT, Fuenger S, Rehrauer WM, Jing P, Rudersdorf RR, Liebl ME, Krebs K, Vasquez J, Dodds E, Loffredo J, Martin S, McDermott AB, Allen TM, Wang C, Doxiadis GG, Montefiori DC, Hughes A, Burton DR, Allison DB, Wolinsky SM, Bontrop R, Picker LJ, Watkins DI (2003) Major histocompatibility complex class I alleles associated with slow simian immunodeficiency virus disease progression bind epitopes recognized by dominant acute-phase cytotoxic–T-lymphocyte responses. J Virol 77:9029–9040PubMedCrossRefGoogle Scholar
- 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 79:8878–8885PubMedCrossRefGoogle Scholar
- Slierendregt BL, Hall M, ’t Hart B, Otting N, Anholts J, Verduin W, Claas F, Jonker M, Lanchbury JS, Bontrop RE (1995a) Identification of an Mhc-DPB1 allele involved in susceptibility to experimental autoimmune encephalomyelitis in rhesus macaques. Int Immunol 7:1671–1679PubMedCrossRefGoogle Scholar
- Rhesus Macaque Genome Sequencing and Analysis Consortium (2007) The rhesus macaque genome sequence informs biomedical and evolutionary analyses. Science (in press)Google Scholar
- Yant LJ, Friedrich TC, Johnson RC, May GE, Maness NJ, Enz AM, Lifson JD, O’connor DH, Carrington M, Watkins DI (2006) The high-frequency major histocompatibility complex class I allele Mamu-B*17 is associated with control of simian immunodeficiency virus SIVmac239 replication. J Virol 80:5074–5077PubMedCrossRefGoogle Scholar
- Yoshioka T, Ageyama N, Shibata H, Yasu T, Misawa Y, Takeuchi K, Matsui K, Yamamoto K, Terao K, Shimada K, Ikeda U, Ozawa K, Hanazono Y (2005) Repair of infarcted myocardium mediated by transplanted bone marrow-derived CD34+ stem cells in a nonhuman primate model. Stem Cells 23:355–364PubMedCrossRefGoogle Scholar