Abstract
Sharks are the most ancient group of vertebrates known to possess members of the major histocompatibility complex (MHC) gene family. For this reason, sharks provide a unique opportunity to gain insight into the evolution of the vertebrate immune system through comparative analysis. Two genes encoding proteins related to the MHC class I gene family were isolated from splenic cDNA derived from spiny dogfish shark (Squalus acanthias). The genes have been designated MhcSqac-UAA*01 and MhcSqac-UAA*NC1. Comparative analysis demonstrates that the Sqac-UAA*01 protein sequence clusters with classical MHC class I of several shark species and has structural elements common to most classical MHC class I molecules. In contrast, Sqac-UAA*NC1 is highly divergent from all vertebrate classical MHC class I proteins, including the Sqac-UAA*01 sequence and those of other shark species. Although Sqac-UAA*NC1 is clearly related to the MHC class I gene family, no orthologous genes from other species were identified due to the high degree of sequence divergence. In fact, the Sqac NC1 protein sequence is the most divergent MHC class-I-like protein identified thus far in any shark species. This high degree of divergence is similar in magnitude to some of the MHC class-I-related genes found in mammals, such as MICA or CD1. These data support the existence of a class of highly divergent non-classical MHC class I genes in the most primitive vertebrates known to possess homologues of the MHC and other components of the adaptive immune system.
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References
Bahram S, Mizuki N, Inoko H, Spies T (1996) Nucleotide sequence of the human MHC class I MICA gene. Immunogenetics 44:80–81
Bartl S, Weissman IL (1994a) Isolation and characterization of major histocompatibility complex class IIB genes from the nurse shark. Proc Natl Acad Sci USA 91:262–266
Bartl S, Weissman IL (1994b) The isolation of putative major histocompatibility complex gene fragments from dogfish and nurse shark. Ann N Y Acad Sci 712:346–349
Bartl S, Baish MA, Flajnik MF, Ohta Y (1997) Identification of class I genes in cartilaginous fish, the most ancient group of vertebrates displaying an adaptive immune response. J Immunol 159:6097–6104
Bauer S, Groh V, Wu J, Steinle A, Phillips JH, Lanier LL, Spies T (1999) Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science 285:727–729
Betz UA, Mayer WE, Klein J (1994) Major histocompatibility complex class I genes of the coelacanth Latimeria chalumnae. Proc Natl Acad Sci USA 91:11065–11069
Carroll MC, Katzman P, Alicot EM, Koller BH, Geraghty DE, Orr HT, Strominger JL, Spies T (1987) Linkage map of the human major histocompatibility complex including the tumor necrosis factor genes. Proc Natl Acad Sci USA 84:8535–8539
Groh V, Steinle A, Bauer S, Spies T (1998) Recognition of stress-induced MHC molecules by intestinal epithelial gammadelta T cells. Science 279:1737–1740
Hinds KR, Litman GW (1986) Major reorganization of immunoglobulin VH segmental elements during vertebrate evolution. Nature 320:546–549
Hughes AL (1991) Evolutionary origin and diversification of the mammalian CD1 antigen genes. Mol Biol Evol 8:185–201
Kasahara M, Vazquez M, Sato K, McKinney EC, Flajnik MF (1992) Evolution of the major histocompatibility complex: isolation of class II A cDNA clones from the cartilaginous fish. Proc Natl Acad Sci USA 89:6688–6692
Klein J, Bontrop RE, Dawkins RL, Erlich HA, Gyllensten UB, Heise ER, Jones PP, Parham P, Wakeland EK, Watkins DI (1990) Nomenclature for the major histocompatibility complexes of different species: a proposal. Immunogenetics 31:217–219
Kruiswijk CP, Hermsen TT, Westphal AH, Savelkoul HF, Stet RJ (2002) A novel functional class I lineage in zebrafish (Danio rerio), carp (Cyprinus carpio), and large barbus (Barbus intermedius) showing an unusual conservation of the peptide binding domains. J Immunol 169:1936–1947
Leishman AJ, Naidenko OV, Attinger A, Koning F, Lena CJ, Xiong Y, Chang HC, Reinherz E, Kronenberg M, Cheroutre H (2001) T cell responses modulated through interaction between CD8alphaalpha and the nonclassical MHC class I molecule, TL. Science 294:1936–1939
Madden DR, Gorga JC, Strominger JL, Wiley DC (1992) The three-dimensional structure of HLA-B27 at 2.1 Å resolution suggests a general mechanism for tight peptide binding to MHC. Cell 70:1035–1048
Mellman I (1996) Endocytosis and molecular sorting. Annu Rev Cell Dev Biol 12:575–625
Ohta Y, McKinney EC, Criscitiello MF, Flajnik MF (2002) Proteasome, transporter associated with antigen processing, and class I genes in the nurse shark Ginglymostoma cirratum: evidence for a stable class I region and MHC haplotype lineages. J Immunol 168:771–81
Porcelli SA (1995) The CD1 family: a third lineage of antigen-presenting molecules. Adv Immunol 59:1–98
Porcelli SA, Segelke BW, Sugita M, Wilson IA, Brenner MB (1998) The CD1 family of lipid antigen-presenting molecules. Immunol Today 19:362–368
Rast JP, Anderson MK, Strong SJ, Luer C, Litman RT, Litman GW (1997) Alpha, beta, gamma, and delta T cell antigen receptor genes arose early in vertebrate phylogeny. Immunity 6:1–11
Shum BP, Rajalingam R, Magor KE, Azumi K, Carr WH, Dixon B, Stet RJ, Adkison MA, Hedrick RP, Parham P (1999) A divergent non-classical class I gene conserved in salmonids. Immunogenetics 49:479–490
Simister NE, Mostov KE (1989) An Fc receptor structurally related to MHC class I antigens. Nature 337:184–187
Sugita M, Jackman RM, van Donselaar E, Behar SM, Rogers RA, Peters PJ, Brenner MB, Porcelli SA (1996) Cytoplasmic tail-dependent localization of CD1b antigen-presenting molecules to MIICs. Science 273:349–52
Acknowledgements
The authors would like to thank Drs. Simona Bartl and Jon Higgins for critical review of the manuscript and Andrew Sexton of the Woods Hole Marine Biological Laboratory for assistance in obtaining samples.
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The nucleotide sequences are available in GenBank, with accession numbers AY150811 (MhcSqac-UAA*01) and AF515705 (MhcSqac-UAA*NC1)
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Wang, C., Perera, T.V., Ford, H.L. et al. Characterization of a divergent non-classical MHC class I gene in sharks. Immunogenetics 55, 57–61 (2003). https://doi.org/10.1007/s00251-003-0542-4
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DOI: https://doi.org/10.1007/s00251-003-0542-4