, 63:619 | Cite as

Characterisation of Mhc class I and class II DRB polymorphism in red-bellied tamarins (Saguinus labiatus)

  • Edward T. Mee
  • James Greenhow
  • Nicola J. Rose
Original Paper


The infection of red-bellied tamarins (Saguinus labiatus) with GB virus B (GBV-B) is an important surrogate model of hepatitis C virus infection in man. To fully exploit the value of this model, we have characterised MHC class I G and class II DRB alleles in eight tamarins representing a cross-section of a UK breeding colony. The results indicated a high degree of classes I and II DRB allele sharing. Each animal transcribed three to four putative surface-expressed class I alleles and two to four class II DRB alleles. Most animals also transcribed at least one class I allele predicted to result in a C-terminal truncated protein. These results represent the first description of MHC polymorphism in this species and provide a foundation for characterisation of MHC diversity in breeding populations of red-bellied tamarins. The data will facilitate the identification of associations between MHC polymorphism and control of viral infections, and detailed dissection of cellular immune responses against GBV-B.


Tamarin Saguinus labiatus New World monkey GBV-B MHC 



We are grateful to Jessica Dale for helpful discussions and provision of biological samples from tamarins and to the veterinary and support staff for their expertise. This work was funded by the NIHR Centre for Research in Health Protection at the Health Protection Agency. This report is of work commissioned by the National Institute for Health Research. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.


  1. Almarri A, El Dwick N, Al Kabi S, Sleem K, Rashed A, Ritter MA, Batchelor JR (1998) Interferon-alpha therapy in HCV hepatitis: HLA phenotype and cirrhosis are independent predictors of clinical outcome. Hum Immunol 59:239–242PubMedCrossRefGoogle Scholar
  2. Alric L, Fort M, Izopet J, Vinel JP, Charlet JP, Selves J, Puel J, Pascal JP, Duffaut M, Abbal M (1997) Genes of the major histocompatibility complex class II influence the outcome of hepatitis C virus infection. Gastroenterology 113:1675–1681PubMedCrossRefGoogle Scholar
  3. Benirschke K, Anderson JM, Brownhill LE (1962) Marrow chimerism in marmosets. Science 138:513–515PubMedCrossRefGoogle Scholar
  4. Bowen DG, Walker CM (2005) Adaptive immune responses in acute and chronic hepatitis C virus infection. Nature 436:946–952PubMedCrossRefGoogle Scholar
  5. Bright H, Carroll AR, Watts PA, Fenton RJ (2004) Development of a GB virus B marmoset model and its validation with a novel series of hepatitis C virus NS3 protease inhibitors. J Virol 78:2062–2071PubMedCrossRefGoogle Scholar
  6. Bukh J, Apgar CL, Yanagi M (1999) Toward a surrogate model for hepatitis C virus: an infectious molecular clone of the GB virus-B hepatitis agent. Virology 262:470–478PubMedCrossRefGoogle Scholar
  7. Bukh J, Apgar CL, Govindarajan S, Purcell RH (2001) Host range studies of GB virus-B hepatitis agent, the closest relative of hepatitis C virus, in New World monkeys and chimpanzees. J Med Virol 65:694–697PubMedCrossRefGoogle Scholar
  8. Cropp SJ, Larson A, Cheverud JM (1999) Historical biogeography of tamarins, genus Saguinus: the molecular phylogenetic evidence. Am J Phys Anthropol 108:65–89PubMedCrossRefGoogle Scholar
  9. Fanning LJ, Levis J, Kenny-Walsh E, Whelton M, O'Sullivan K, Shanahan F (2001) HLA class II genes determine the natural variance of hepatitis C viral load. Hepatology 33:224–230PubMedCrossRefGoogle Scholar
  10. Griffin S, Trowbridge R, Thommes P, Parry N, Rowlands D, Harris M, Bright H (2008) Chimeric GB virus B genomes containing hepatitis C virus p7 are infectious in vivo. J Hepatol 49:908–915PubMedCrossRefGoogle Scholar
  11. Gyllensten U, Bergstrom T, Josefsson A, Sundvall M, Savage A, Blumer ES, Giraldo LH, Soto LH, Watkins DI (1994) The cotton-top tamarin revisited: Mhc class I polymorphism of wild tamarins, and polymorphism and allelic diversity of the class II DQA1, DQB1, and DRB loci. Immunogenetics 40:167–176PubMedCrossRefGoogle Scholar
  12. Haqshenas G, Dong X, Netter H, Torresi J, Gowans EJ (2007) A chimeric GB virus B encoding the hepatitis C virus hypervariable region 1 is infectious in vivo. J Gen Virol 88:895–902PubMedCrossRefGoogle Scholar
  13. Jacob JR, Lin K-C, Tennant BC, Mansfield KG (2004) GB virus B infection of the common marmoset (Callithrix jacchus) and associated liver pathology. J Gen Virol 85:2525–2533PubMedCrossRefGoogle Scholar
  14. Kuniholm MH, Kovacs A, Gao X, Xue X, Marti D, Thio CL, Peters MG, Terrault NA, Greenblatt RM, Goedert JJ, Cohen MH, Minkoff H, Gange SJ, Anastos K, Fazzari M, Harris TG, Young MA, Strickler HD, Carrington M (2010) Specific human leukocyte antigen class I and II alleles associated with hepatitis C virus viremia. Hepatology 51:1514–1522PubMedCrossRefGoogle Scholar
  15. Lanford RE, Chavez D, Notvall L, Brasky KM (2003) Comparison of tamarins and marmosets as hosts for GBV-B infections and the effect of immunosuppression on duration of viremia. Virology 311:72–80PubMedCrossRefGoogle Scholar
  16. McKiernan SM, Hagan R, Curry M, McDonald GS, Kelly A, Nolan N, Walsh A, Hegarty J, Lawlor E, Kelleher D (2004) Distinct MHC class I and II alleles are associated with hepatitis C viral clearance, originating from a single source. Hepatology 40:108–114PubMedCrossRefGoogle Scholar
  17. Rijnbrand R, Yang Y, Beales L, Bodola F, Goettge K, Cohen L, Lanford RE, Lemon SM, Martin A (2005) A chimeric GB virus B with 5′ nontranslated RNA sequence from hepatitis C virus causes hepatitis in tamarins. Hepatology 41:986–994PubMedCrossRefGoogle Scholar
  18. Robinson J, Waller MJ, Parham P, de Groot N, Bontrop R, Kennedy LJ, Stoehr P, Marsh SG (2003) IMGT/HLA and IMGT/MHC: sequence databases for the study of the major histocompatibility complex. Nucleic Acids Res 31:311–314PubMedCrossRefGoogle Scholar
  19. Robinson J, Waller MJ, Stoehr P, Marsh SG (2005) IPD—the immuno polymorphism database. Nucleic Acids Res 33:D523–D526PubMedCrossRefGoogle Scholar
  20. Romero-Gomez M, Gonzalez-Escribano MF, Torres B, Barroso N, Montes-Cano MA, Sanchez-Munoz D, Nunez-Roldan A, Aguilar-Reina J (2003) HLA class I B44 is associated with sustained response to interferon + ribavirin therapy in patients with chronic hepatitis C. Am J Gastroenterol 98:1621–1626PubMedGoogle Scholar
  21. Ross CN, French JA, Orti G (2007) Germ-line chimerism and paternal care in marmosets (Callithrix kuhlii). Proc Natl Acad Sci USA 104:6278–6282PubMedCrossRefGoogle Scholar
  22. Tamura K, Dudley J, Nei M, Kumar S (2007) MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. Mol Biol Evol 24:1596–1599PubMedCrossRefGoogle Scholar
  23. Thio CL, Gao X, Goedert JJ, Vlahov D, Nelson KE, Hilgartner MW, O'Brien SJ, Karacki P, Astemborski J, Carrington M, Thomas DL (2002) HLA-Cw*04 and hepatitis C virus persistence. J Virol 76:4792–4797PubMedCrossRefGoogle Scholar
  24. Wang LY, Lin HH, Lee TD, Wu YF, Hu CT, Cheng ML, Lo SY (2005) Human leukocyte antigen phenotypes and hepatitis C viral load. J Clin Virol 32:144–150PubMedCrossRefGoogle Scholar
  25. Watkins DI, Hodi FS, Letvin NL (1988a) A primate species with limited major histocompatibility complex class I polymorphism. Proc Natl Acad Sci USA 85:7714–7718PubMedCrossRefGoogle Scholar
  26. Watkins DI, Kannagi M, Stone ME, Letvin NL (1988b) Major histocompatibility complex class I molecules of nonhuman primates. Eur J Immunol 18:1425–1432PubMedCrossRefGoogle Scholar
  27. Watkins DI, Chen ZW, Hughes AL, Evans MG, Tedder TF, Letvin NL (1990a) Evolution of the MHC class I genes of a New World primate from ancestral homologues of human non-classical genes. Nature 346:60–63PubMedCrossRefGoogle Scholar
  28. Watkins DI, Letvin NL, Hughes AL, Tedder TF (1990b) Molecular cloning of cDNA that encode MHC class I molecules from a New World primate (Saguinus oedipus). Natural selection acts at positions that may affect peptide presentation to T cells. J Immunol 144:1136–1143PubMedGoogle Scholar
  29. Watkins DI, Garber TL, Chen ZW, Toukatly G, Hughes AL, Letvin NL (1991) Unusually limited nucleotide sequence variation of the expressed major histocompatibility complex class I genes of a New World primate species (Saguinus oedipus). Immunogenetics 33:79–89PubMedGoogle Scholar
  30. Woollard DJ, Haqshenas G, Dong X, Pratt BF, Kent SJ, Gowans EJ (2008) Virus-specific T-cell immunity correlates with control of GB virus B infection in marmosets. J Virol 82:3054–3060PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Edward T. Mee
    • 1
  • James Greenhow
    • 1
  • Nicola J. Rose
    • 1
  1. 1.Division of Retrovirology, National Institute for Biological Standards and ControlHealth Protection AgencyHertfordshireUK

Personalised recommendations