Abstract
Few studies have yet addressed the functional aspects of MHC molecules in fish. To lay the foundation for this, we evaluated the association between disease resistance and MHC class I and class II polymorphism in Atlantic salmon. Standardized disease challenge trials were performed on a semi-wild Atlantic salmon population with subsequent MHC typing and statistical analysis. The pathogens employed were infectious salmon anaemia virus (ISAV) causing infectious salmon anaemia and the Aeromonas salmonicida bacteria causing furunculosis. The material consisted of 1,182 Atlantic salmon from 33 families challenged with A. salmonicida and 1,031 Atlantic salmon from 25 families challenged with ISAV. We found highly significant associations between resistance towards infectious diseases caused by both pathogens and MH class I and class II polymorphism in Atlantic salmon. The observed associations were detected due to independently segregating MH class I and class II single loci, and inclusion of a large number of fish allowing an extensive statistical analysis.
Similar content being viewed by others
References
Agresti (1990) Categorical Data Analysis. Wiley, New York
Aoyagi K, Dijkstra JM, Xia C, Denda I, Ototake M, Hashimoto K, Nakanishi T (2002) Classical MHC class I genes composed of highly divergent sequence lineages share a single locus in rainbow trout (Oncorhynchus mykiss). J Immunol 168:260–273
Bacon LD (1987) Influence of the major histocompatibility complex on disease resistance and productivity. Poult Sci 66:802–811
Bacon LD, Hunt HD, Cheng HH (2000) A review of the development of chicken lines to resolve genes determining resistance to diseases. Poult Sci 79:1082–1093
Bot A, Casares S, Bot S, von Boehmer H, Bona C (1998) Cellular mechanisms involved in protection against influenza virus infection in transgenic mice expressing a TCR receptor specific for class II hemagglutinin peptide in CD4+ and CD8+ T cells. J Immunol 160:4500–4507
Carrington M, O'Brien SJ (2003) The influence of HLA genotype on AIDS. Annu Rev Med 54:535–551
Cheng HH, Levin I, Vallejo RL, Khatib H, Dodgson JB, Crittenden LB, Hillel J (1995) Development of a genetic map of the chicken with markers of high utility. Poult Sci 74:1855–1874
Clouthier SC, Rector T, Brown NE, Anderson ED (2002) Genomic organization of infectious salmon anaemia virus. J Gen Virol 83:421–8
Douglas GA (1991) Practical statistics for medical research. Chapman and Hall, London
Egidius E (1987) Import of furunculosis to Norway with Atlantic salmon smolts from Scotland. International Council for the Exploration of the sea (ICES). Mariculture Committee C.M.1987/F:8. Report
Emmerich R, Weibel E (1894) Ueber eine durch bakterien erzengte seuche unter den forellen. Arch Hyg Bacteriol 21:1–21
Falk K, Namork E, Rimstad E, Mjaaland S, Dannevig BH (1997) Characterization of infectious salmon anemia virus, an orthomyxo-like virus isolated from Atlantic salmon (Salmo salar L.). J Virol 71:9016–9023
Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA, Basava A, Dormishian F, Domingo R Jr, Ellis MC, Fullan A, Hinton LM, Jones NL, Kimmel BE, Kronmal GS, Lauer P, Lee VK, Loeb DB, Mapa FA, McClelland E, Meyer NC, Mintier GA, Moeller N, Moore T, Morikang E, Wolff RK, et al. (1996) A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 13:399–408
Garduno RA, Moore AR, Olivier G, Lizama AL, Garduno E, Kay WW (2000) Host cell invasion and intracellular residence by Aeromonas salmonicida: role of the S-layer. Can J Microbiol 46:660–668
Gjedrem T (2000) Genetic improvement of cold-water fish species. Aquaculture 31:25–33
Gjedrem T, Gjoen HM, Gjerde B (1991) Genetic origin of Norwegian farmed Atlantic salmon. Aquaculture 98:41–50
Graser R, O'hUigin C, Vincek V, Meyer A, Klein J (1996) Trans-species polymorphism of class II Mhc loci in danio fishes. Immunogenetics 44:36–48
Grimholt U, Hordvik I, Fosse VM, Olsaker I, Endresen C, Lie O (1993) Molecular cloning of major histocompatibility complex class I cDNAs from Atlantic salmon (Salmo salar). Immunogenetics 37:469–473
Grimholt U, Getahun A, Hermsen T, Stet RJ (2000) The major histocompatibility class II alpha chain in salmonid fishes. Dev Comp Immunol 24:751–63
Grimholt U, Drabløs F, Jørgensen SM, Høyheim B, Stet RJM (2002) The major histocompatibility class I locus in Atlantic salmon (Salmo salar L.): polymorphism, linkage analysis and protein modelling. Immunogenetics 54:570–581
Hansen JD, Strassburger P, Thorgaard GH, Young WP, Du PL (1999) Expression, linkage, and polymorphism of MHC-related genes in rainbow trout, Oncorhynchus mykiss. J Immunol 163:774–86
Harris EK, Albert A (1991) Survivorship analysis for clinical studies. Dekker, New York
Hashimoto K, Nakanishi T, Kurosawa Y (1990) Isolation of carp genes encoding major histocompatibility complex antigens. Proc Natl Acad Sci USA 87:6863-6867
Hill AV (1998) The immunogenetics of human infectious diseases. Annu Rev Immunol 16:593–617
Hill AV, Yates SN, Allsopp CE, Gupta S, Gilbert SC, Lalvani A, Aidoo M, Davenport M, Plebanski M (1994) Human leukocyte antigens and natural selection by malaria. Philos Trans R Soc Lond B Biol Sci 346:379–385
Hordvik I, Grimholt U, Fosse VM, Lie O, Endresen C (1993) Cloning and sequence analysis of cDNAs encoding the MHC class II beta chain in Atlantic salmon (Salmo salar). Immunogenetics 37:437–441
Jacob JP, Milne S, Beck S, Kaufman J (2000) The major and a minor class II beta-chain (B-LB) gene flank the Tapasin gene in the B-F/B-L region of the chicken major histocompatibility complex. Immunogenetics 51:138–147
Kaufman J, Milne S, Gobel TW, Walker BA, Jacob JP, Auffray C, Zoorob R, Beck S (1999) The chicken B locus is a minimal essential major histocompatibility complex. Nature 401:923–925
Krossoy B, Nilsen F, Falk K, Endresen C, Nylund A (2001) Phylogenetic analysis of infectious salmon anaemia virus isolates from Norway, Canada and Scotland. Dis Aquat Organ 44:1–6
Lamont SJ (1998) The chicken major histocompatibility complex and disease. Rev Sci Tech 17:128–142
Langefors A, Lohm J, Grahn M, Andersen O, von Schantz T (2001) Association between major histocompatibility complex class IIB alleles and resistance to Aeromonas salmonicida in Atlantic salmon. Proc R Soc Lond B Biol Sci 268:479–485
Lehmann EL (1975) Non-parametrics: statistical methods based on ranks. Holden-Day, San Fransisco
Marsh SGE, Parham P, Barber LD (2000) The HLA factsbook. San Diego
Martinez-Borra J, Gonzalez S, Lopez-Vazquez A, Gelaz MA, Armas JB, Kanga U, Mehra NK, Lopez-Larrea C (2000) HLA-B27 alone rather than B27-related class I haplotypes contributes to ankylosing spondylitis susceptibility. Hum Immunol 61:131–139
Mjaaland S, Rimstad E, Falk K, Dannevig BH (1997) Genomic characterization of the virus causing infectious salmon anemia in Atlantic salmon (Salmo salar L.): an orthomyxo-like virus in a teleost. J Virol 71:7681–7686
Mullins JE, Groman D, Wadowska D (1998) Infectious salmon anaemia in salt water Atlantic salmon (Salmo salar L.) in New Brunswick, Canada. Bull Eur Assoc Fish Pathol 18:110–114
Nakanishi T, Aoyagi K, Xia C, Dijkstra JM, Ototake M (1999) Specific cell-mediated immunity in fish. Vet Immunol Immunopathol 72:101–109
Nordmo R (1997) Strengths and weaknesses of different challenge methods. In: Gudding R, Lillehaug A, Midtlyng P, Brown F (eds): Fish Vaccinology. Karger, Basel, pp 303–309
Nordmo R, Ramstad A, Riseth JMH (1998) Induction of experimental furunculosis in heterogeneous test populations of Atlantic salmon (Salmo salar L.) by use of a cohabitation method. Aquaculture 162:11–21
Ozaki A, Sakamoto T, Khoo S, Nakamura K, Coimbra MR, Akutsu T, Okamoto N (2001) Quantitative trait loci (QTLs) associated with resistance/susceptibility to infectious pancreatic necrosis virus (IPNV) in rainbow trout (Oncorhynchus mykiss). Mol Genet Genomics 265:23–31
Parham P, Ohta T (1996) Population biology of antigen presentation by MHC class I molecules. Science 272:67–74
Pocock SJ (1983) Clinical trials: a practical approach. Wiley, New York
Puel A, Mevel JC, Bouthillier Y, Feingold N, Fridman WH, Mouton D (1996) Toward genetic dissection of high and low antibody responsiveness in Biozzi mice. Proc Natl Acad Sci USA 93:14742–14746
Raynard RS, Murray AG, Gregory A (2001) Infectious salmon anaemia virus in wild fish from Scotland. Dis Aquat Organ 46:93–100
Rodger HD, Turnbull T, Muir F, Millar S, Richards RH (1998) Infectious salmon anaemia (ISA) in the United Kingdom. Bull Eur Assoc Fish Pathol 18:115–116
Sakamoto T, Danzmann RG, Gharbi K, Howard P, Ozaki A, Khoo SK, Woram RA, Okamoto N, Ferguson MM, Holm LE, Guyomard R, Hoyheim B (2000) A microsatellite linkage map of rainbow trout (Oncorhynchus mykiss) characterized by large sex-specific differences in recombination rates. Genetics 155:1331–1345
Sato A, Figueroa F, Murray BW, Malaga-Trillo E, Zaleska-Rutczynska Z, Sultmann H, Toyosawa S, Wedekind C, Steck N, Klein J (2000) Nonlinkage of major histocompatibility complex class I and class II loci in bony fishes. Immunogenetics 51:108–116
Satta Y, O'hUigin C, Takahata N, Klein J (1994) Intensity of natural selection at the major histocompatibility complex loci. Proc Natl Acad Sci USA 91:7184–7188
Shum BP, Guethlein L, Flodin LR, Adkison MA, Hedrick RP, Nehring RB, Stet RJ, Secombes C, Parham P (2001) Modes of salmonid MHC class I and II evolution differ from the primate paradigm. J Immunol 166:3297–3308
Stet RJM, de Vries B, Mudde K, Hermsen TT, van Heerwaarden J, Shum BP, Grimholt U (2002) Unique haplotypes of co-segregating major histocompatibility class II A and class II B alleles in Atlantic salmon (Salmo salar) give rise to diverse class II genotypes. Immunogenetics 54:320–331
Takami K, Zaleska-Rutczynska Z, Figueroa F, Klein J (1997) Linkage of LMP, TAP, and RING3 with Mhc class I rather than class II genes in the zebrafish. J Immunol 159:6052–6060
The MHC Sequencing Consortium (1999) Complete sequence and gene map of a human major histocompatiblity complex. Nature 401:921–923
Thorud K, Djupvik HO (1988) Infectious anaemia in Atlantic salmon (Salmo salar L.). Bull Eur Ass Fish Pathol 8:111
Vallejo RL, Bacon LD, Liu HC, Witter RL, Groenen MA, Hillel J, Cheng HH (1998) Genetic mapping of quantitative trait loci affecting susceptibility to Marek's disease virus induced tumors in F2 intercross chickens. Genetics 148:349–360
Yonash N, Bacon LD, Witter RL, Cheng HH (1999) High resolution mapping and identification of new quantitative trait loci (QTL) affecting susceptibility to Marek's disease. Anim Genet 30:126–135
Acknowledgements
This study was supported by a grant from the European Commission (Fair CT97-3643). All animal experiments performed in this study comply with the current laws of Norway. We would like to thank Beja de Vries, Karin Mudde, Trudi Hermsen, Elin Urdahl, Siv Malme, Eirik Balgaard, Sven Martin Jørgensen and Christian Gløckner for their excellent technical support. The nucleotide sequences in this study are available upon request for research purposes.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Grimholt, U., Larsen, S., Nordmo, R. et al. MHC polymorphism and disease resistance in Atlantic salmon (Salmo salar); facing pathogens with single expressed major histocompatibility class I and class II loci. Immunogenetics 55, 210–219 (2003). https://doi.org/10.1007/s00251-003-0567-8
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00251-003-0567-8