Skip to main content

Advertisement

SpringerLink
Log in

Class II multiformity generated by variable MHC-DRB region configurations in the California sea lion (Zalophus californianus)

  • Original Paper
  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

In light of the immunological importance of molecules encoded within the major histocompatibility complex (MHC), there are numerous studies examining the variability of these genes in wildlife populations. An underlying assumption in many of these studies is that MHC diversity invariably arises from a high level of allelic variation at a single gene locus, leading to widespread descriptions of thriving species with apparently limited MHC polymorphism. Indeed, in a previous study we failed to find sequence features compatible with traditionally diverse peptide-binding functions in MHC class II (DQA and DQB) genes in California sea lions and therefore expanded the search for polymorphism to the DRA and DRB genes. Our results show that, in contrast to Zaca-DQA, -DQB, and -DRA, Zaca-DRB has sequence features compatible with antigen binding and presentation. In fact Zaca-DRB constitutes a gene family, comprising at least seven loci, each of which exhibits limited variability, and which are present in variable configurations between individuals. This unusual mechanism for generating MHC DRB diversity is similar to that observed in the rhesus macaque, but has not been reported in any other species. The identification of a novel system of class II MHC variability in the California sea lion justifies new studies into the organizational basis of immunogenetic diversity in other marine species, and its role in infectious disease susceptibility.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215:403–410

    Article  CAS  PubMed  Google Scholar 

  • Bodmer JG, Marsh SGE, Albert ED, Bodmer WF, Bontrop RE, et al (1999) Nomenclature for factors of the HLA system, 1998. Tissue Antigens 53:407–446

    CAS  Google Scholar 

  • Bontrop RE, Otting N, de Groot NG, Doxiadis GGM (1999) Major histocompatibility complex class II polymorphisms in primates. Immunol Rev 167:339–350

    CAS  PubMed  Google Scholar 

  • Bowen L, Aldridge BM, Stott JL, Gulland F, Woo J, Van Bonn W, DeLong R, Lowenstine L, Johnson ML (2002) Molecular characterization of expressed DQA and DQB genes in the California sea lion (Zalophus californianus). Immunogenetics 54:332–347

    Article  CAS  PubMed  Google Scholar 

  • Brown JH, Jardetzky TS, Gorga JC, Stern LJ, Urban RG, et al (1993) Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1. Nature 364:33–39

    CAS  PubMed  Google Scholar 

  • Calkins DG, McAllister DC, Pitcher KW (1999) Steller sea lions status and trend in Southeast Alaska: 1979–1997. Marine Mamm Sci 15:462–477

    Google Scholar 

  • Doxiadis GG, Otting N, de Groot NG, Bontrop RE (2001) Differential evolutionary MHC class II strategies in humans and rhesus macaques: relevance for biomedical studies. Immunol Rev 183:76–85

    Article  CAS  PubMed  Google Scholar 

  • Erlich HA, Gyllensten UB (1991) Shared epitopes among HLA class II alleles, gene conversion, common ancestry and balancing selection. Immunol Today 12:411–414

    CAS  Google Scholar 

  • Escayg AP, Hickford JGH, Montgomery GW, Dodds KG, Bullock DW (1996) Polymorphism at the ovine major histocompatibility complex class II loci. Anim Genet 27:305–312

    CAS  PubMed  Google Scholar 

  • Fabb SA, Maddox JF, Gogolinewens KJ, Baker L, Wu MJ, Brandon MR (1993) Isolation, Characterization and evolution of ovine major histocompatibility complex class-II Dra and Dqa genes. Anim Genet 24:249–255

    CAS  PubMed  Google Scholar 

  • Fan W, Gutknecht J, Klein D, Mayer WE, Jonker M, Klein J (1989) Shared class II MHC polymorphisms between humans and chimpanzees. Hum Immunol 26:107–121

    CAS  Google Scholar 

  • Felsenstein J (1993) PHYLIP: phylogenetic inference package version 3.5c. University of Washington, Seattle, Washington, USA

  • Gaur LK, Nepom GT (1996) Ancestral major histocompatibility complex DRB genes beget conserved patterns of localized polymorphisms. Proc Natl Acad Sci U S A 93:5380–5383

  • Gilmartin WG, Johanos TC, Eberhardt LL (1993) Survival rates for the Hawaiian monk seal (Monachus schauinslandi). Mar Mamm Sci 9:407–420

    Google Scholar 

  • Gulland FMD, Koski M, Lowenstine LJ, Colagross A, Morgan L, Spraker T (1996) Leptospirosis in California sea lions (Zalophus californianus) stranded along the central California coast, 1981–1994. J Wildl Dis 32:572–580

    CAS  PubMed  Google Scholar 

  • Gustafsson K, Germana S, Hirsch F, Pratt K, LeGuern C, Sachs DH (1990) Structure of miniature swine class II DRB genes: Conservation of hypervariable amino acid residues between distantly related mammalian species. Immunology 87:9798–9802

    CAS  Google Scholar 

  • Hoelzel AR, Stephens J, O’Brien SJ (1999) Molecular genetic diversity and evolution at the MHC DQB locus in four species of pinnipeds. Mol Biol Evol 16:611–618

    CAS  PubMed  Google Scholar 

  • Kennedy MC, Wang J, Zhang Y, Miles AP, Chitsaz F, Saul A, Long CA, Miller LH, Stowers AW (2002) In vitro studies with recombinant Plasmodium falciparum apical membrane antigen 1 (AMA1): production and activity of an AMA1 vaccine and generation of a multiallelic response. Infect Immun 70:6948–6960

    Article  CAS  PubMed  Google Scholar 

  • King DP, Hure MC, Goldstein T, Aldridge BM, Gulland FM, Saliki JT, Buckles EL, Lowenstine LJ, Stott JL (2002) Otarine herpesvirus-1: a novel gammaherpesvirus associated with urogenital carcinoma in California sea lions (Zalophus californianus). Vet Microbiol 86:131–137

    Article  CAS  PubMed  Google Scholar 

  • Klein J, Sato A (2000a) The HLA system: First of two parts. N Engl J Med 343:702–709

    CAS  PubMed  Google Scholar 

  • Klein J, Sato A (2000b) The HLA system: Second of two parts. N Engl J Med 343:782–786

    CAS  Google Scholar 

  • Klein J, Takahata N (1990) The major histocompatibility complex and the quest for origins. Immunol Rev 113:5–26

    CAS  PubMed  Google Scholar 

  • Klein J, Figueroa F, Cohen N (1986) Evolution of the major histocompatibility complex. Crit Rev Immunol 6:295–386

    CAS  Google Scholar 

  • Kumar S, Tamura K, Jakobsen I, Nei M (2001) MEGA2: molecular evolutionary genetics analysis software. Bioinformatics 17:1244–1245

    CAS  PubMed  Google Scholar 

  • Ledje C, Arnason U (1996) Phylogenetic analyses of complete cytochrome b genes of the order carnivora with particular emphasis on the caniformia. J Mol Evol 42:135–144

    CAS  PubMed  Google Scholar 

  • Lyons ET, Melin SR, DeLong RL, Orr AJ, Gulland FM, Tolliver SC (2001) Current prevalence of adult Uncinaria spp. in northern fur seal (Callorhinus ursinus) and California sea lion (Zalophus californianus) pups on San Miguel Island, California, with notes on the biology of these hookworms. Vet Parasitol 97:309–318

    Article  CAS  PubMed  Google Scholar 

  • Mikko S, Spencer M, Morris B, Stabile S, Basu T, et al (1997) A comparative analysis of MHC DRB3 polymorphism in the American bison (Bison bison). J Hered 88:499–503

    CAS  PubMed  Google Scholar 

  • Mikko S, Roed K, Schmutz S, Andersson L (1999) Monomorphism and polymorphism at MHC DRB loci in domestic and wild ruminants. Immunol Rev 167:169–178

    CAS  Google Scholar 

  • Murray BW, White B (1998) Sequence variation at the major histocompatibility complex DRB loci in beluga (Delphinapterus leucas) and narwhal (Monodon monoceros). Immunogenetics 48:242–252

    Article  CAS  Google Scholar 

  • National Marine Fisheries Service (1995) Status review of the United States Steller sea lion (Eumetopias jubatus) population. (Ref Type: Report) National Marine Mammal Laboratory, NMFS, Seattle, Wash

  • Paterson S, Wilson K, Pemberton JM (1998) Major histocompatibility complex variation associated with juvenile survival and parasite resistance in a large unmanaged ungulate population. Proc Natl Acad Sci U S A 95:3714–3719

  • Paul WE (1999) Fundamental immunology, 4th edn. Lippincott-Raven, Philadelphia

  • Reizis B, Eisenstein M, Mor F, Cohen IR (1998) The peptide-binding strategy of the MHC class II I-A molecules. Immunol Today 19:212–216

    CAS  PubMed  Google Scholar 

  • Robbins F, Hurley CK, Tang T, Yao H, Lin YS, Wade J, Goeken N, Hartzman RJ (1997) Diversity associated with the second expressed HLA-DRB locus in the human population. Immunogenetics 46:104–110

    Article  CAS  PubMed  Google Scholar 

  • Robinson J, Waller M, Parham P, Bodmer JG, Marsh SGE (2001) IMGT/HLA Database — a sequence database for the human major histocompatibility complex. Nucleic Acids Res 29:210–213

    CAS  PubMed  Google Scholar 

  • Sarmiento UM, Sarmiento JI, Storb R (1990) Allelic variation in the DR subregion of the canine major histocompatibility complex. Immunogenetics 32:13–9

    CAS  Google Scholar 

  • Schreiber A, Eulenberger K, Bauer K (1998) Immunogenetic evidence for the phylogenetic sister group relationship of dogs and bears (Mammalia, Carnivora: Canidae and Ursidae), a comparative determinant analysis of carnivoran albumin, c3 complement and immunoglobulin micro-chain. Exp Clin Immunogenet 15:154–170

    CAS  Google Scholar 

  • Slade RW (1992) Limited MHC polymorphism in the southern elephant seal: implications for MHC evolution and marine mammal population biology. Proc R Soc Lond B Biol Sci 249:163–171

    CAS  PubMed  Google Scholar 

  • Slierendregt BL, Van Noort JT, Bakas RM, Otting N, Jonker M, Bontrop RE (1992) Evolutionary stability of transspecies major histocompatibility complex class II DRB lineages in humans and rhesus monkeys. Hum Immunol 35:29–39

    CAS  PubMed  Google Scholar 

  • Stern LJ, Brown JH, Jardetzky TS, Gorga JC, Urban RG, et al (1994) Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide. Nature 368:215–221

    CAS  PubMed  Google Scholar 

  • Svensson A, Setterblad N, Pihlgren U, Rask L, Andersson G (1996) Evolutionary relationship between human major histocompatibility complex HLA-DR haplotypes. Immunogenetics 43:304–314

    Article  CAS  PubMed  Google Scholar 

  • Trites AW, Larkin PA (1996) Changes in the abundance of Stellar sea lions (Eumetopias jubatus) in Alaska from 1956 to 1992: how many were there? Aquatic Mamm 22:153–166

    Google Scholar 

  • Van Den Bussche RA, Hoofer SR, Lochmiller RL (1999) Characterization of MHC-DRB allelic diversity in white-tailed deer (Odocoileus virginianus) provides insight into MHC-DRB allelic evolution with Cervidae. Immunogenetics 49:429–437

    Article  PubMed  Google Scholar 

  • Van Eijk MJ, Stewart-Haynes JA, Lewin HA (1992) Extensive polymorphism of the BoLA-DRB3 gene distinguished by PCR-RFLP. Anim Genet 23:483–496

    PubMed  Google Scholar 

  • Vassetzky NS, Kramerov DA (2002) CAN — a pan-carnivore SINE family. Mamm Genome 13:50–57

    Article  CAS  PubMed  Google Scholar 

  • Wagner JL, Burnett R, Storb R (1996a) Molecular analysis of the DLA DR region. Tissue Antigens 48:549–53

    CAS  PubMed  Google Scholar 

  • Wagner JL, Burnett RC, Works JD, Storb R (1996b) Molecular analysis of DLA-DRBB1 polymorphism. Tissue Antigens 48:554–561

    CAS  PubMed  Google Scholar 

  • Wagner JL, Burnett R, Storb R (1999) Organization of the canine major histocompatibility complex; current perspectives. J Hered 90:35–38

    CAS  PubMed  Google Scholar 

  • Yaeger M, Hughes AL (1999) Evolution of the mammalian MHC: natural selection, recombination, and convergent evolution. Immunol Rev 167:45–58

    PubMed  Google Scholar 

  • Yuhki N, O’Brien S (1997) Nature and origin of polymorphism in feline MHC class II DRA and DRB genes. J Immunol 158:2822–2833

    CAS  PubMed  Google Scholar 

  • Zinkernagel RM (1979) Associations between major histocompatibility antigens and susceptibility to disease. Annu Rev Microbiol 33:201–213

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Brett Russell Smith, Dr. Jodi Hedges, Dr. Elizabeth Buckles, Gina Vittori and members of the Laboratory for Marine Mammal Immunology, University of California-Davis, for their contributions to this project. We would also like to thank Dr. Martin Haulena, Denise Greig, and the staff and volunteers of The Marine Mammal Center, Sausalito, Calif., Tony Orr from the National Marine Mammal Laboratory, Seattle Wash., and Drs. Cynthia Smith and Eric Jensen, and Carrie Lomax from the Navy Marine Mammal Program for help in obtaining the samples used in this study. This study was supported by grants from the Office of Naval Resources Research (N00014-00-14-0763), the Marin Community Foundation, and Ecology of Infectious Disease Program (Fogarty International Center and US National Science Foundation) (DEB-0094919).

Author information

Authors and Affiliations

  1. Laboratory for Marine Mammal Immunology, School of Veterinary Medicine, Department of Pathology, Microbiology and Immunology, University of California, Davis, CA 95616, USA

    Lizabeth Bowen, Brian M. Aldridge, Linda J. Lowenstine & Jeffrey L. Stott

  2. School of Veterinary Medicine, Western Health Sciences University, Pomona, California, USA

    Brian M. Aldridge

  3. The Marine Mammal Center, GGNRA, Marin Headlands, Sausalito, California, USA

    Brian M. Aldridge & Frances Gulland

  4. US Navy Marine Mammal program, SPAWARSYSCEN, San Diego, California, USA

    William Van Bonn

  5. National Marine Mammal Laboratory, NMFS, NOAA, Seattle, Washington, USA

    Robert DeLong & Sharon Melin

  6. John Muir Institute of the Environment, University of California, Davis, California, USA

    Lizabeth Bowen & Michael L. Johnson

Authors
  1. Lizabeth Bowen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brian M. Aldridge
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Frances Gulland
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. William Van Bonn
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Robert DeLong
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sharon Melin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Linda J. Lowenstine
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jeffrey L. Stott
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Michael L. Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lizabeth Bowen.

Additional information

The studies were performed jointly in the laboratories of J.L. Stott and M.L. Johnson

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bowen, L., Aldridge, B.M., Gulland, F. et al. Class II multiformity generated by variable MHC-DRB region configurations in the California sea lion (Zalophus californianus). Immunogenetics 56, 12–27 (2004). https://doi.org/10.1007/s00251-004-0655-4

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00251-004-0655-4

Keywords

Search

Navigation