Abstract
The major histocompatibility complex of cattle (BoLA) contains the class II genes DYA and DIB which are transcribed with a dendritic cell restricted distribution. As part of the process to determine whether these genes have any functional significance, we demonstrate that they form a closely linked pair characteristic of other expressed class II MHC molecules. Accepted nomenclature convention suggests that BoLA-DIB should therefore be renamed BoLA-DYB. Analysis of the first full-length DYA and DYB transcripts revealed open reading frames with potential to translate 253 and 259 amino acid proteins, respectively. Comparative sequence analysis between the DY polypeptides and classical cattle, human and mouse class II MHC α and β polypeptide chains revealed 16 unique amino acid residues at positions predicted to form and line the putative peptide-binding region. Expression of tagged constructs demonstrates for the first time that the DY genes of cattle are capable of translating distinctive class II MHC α and β polypeptide chains.
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References
Alfonso C, Karlsson L (2000) Nonclassical MHC class II molecules. Annu Rev Immunol 18:113–42
Ballingall KT, Dutia BM, Hopkins J, Wright H (1995) Analysis of the fine specificities of sheep major histocompatibility complex class II-specific monoclonal antibodies using mouse L-cell transfectants. Anim Genet 26:79–84
Ballingall KT, MacHugh ND, Taracha ELN, Mertens B, McKeever DJ (2001) Transcription of the unique ruminant class II major histocompatibility complex—DYA and DIB genes in dendritic cells. Eur J Immunol 31:82–86
Bateman A, Birney E, Cerruti L, Durbin R, Etwiller L, Eddy SR, Griffiths-Jones S, Howe KL, Marshall M, Sonnhammer EL (2002) The Pfam protein families database Nucleic Acids Res 30:276–280
Braud V, Jones EY, McMichael A (1997) The human major histocompatibility complex class Ib molecule HLA-E binds signal sequence-derived peptides with primary anchor residues at positions 2 and 9. Eur J Immunol 27:1164–1169
Brown JH, Jardetzky TS, Gorge JC, Stern LJ, Urban RG, Strominger JL, Wiley DC (1993) Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1. Nature 364:33–39
Chowers Y, Holtmeier W, Morzycka-Wroblewska E, Kagnoff MF (1995) Inverse PCR amplification of rare T-cell receptor delta messages from mucosal biopsy specimens. J Immunol Methods 179:261–263
Cosson P, Bonifacino JS (1992) Role of transmembrane domain interactions in the assembly of class II MHC molecules. Science 258:659–662
Di Palma F, Archibald SD, Young JR, Ellis SA (2002) A BAC contig of approximately 400 kb contains the classical class I major histocompatibility complex (MHC) genes of cattle. Eur J Immunogenet 29:65–68
Douek DC, Altmann DM (1997) HLA-DO is an intracellular class II molecule with distinctive thymic expression. Int Immunol 9:355–364
Ellis SA, Ballingall KT (1999) Cattle MHC: evolution in action? Immunol Rev 167:159–168
Emery DL, MacHugh ND, Ellis JA (1987) The properties and functional activity of non-lymphoid cells from cattle afferent lymph. J Immunol 62:177–183
Glass DB, el-Maghrabi MR, Pilkis SJ (1986) Synthetic peptides corresponding to the site phosphorylated in 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase as substrates of cyclic nucleotide-dependent protein kinases. J Biol Chem 261:2987–2993
Hartmann E, Rapoport TA, Lodish HF (1989) Predicting the orientation of eukaryotic membrane-spanning proteins. Proc Natl Acad Sci U S A 86:5786–90
Heijne G von (1986) A new method for predicting signal sequence cleavage sites. Nucleic Acids Res 14:4683–4690
Hennecke J, Carfi A, Wiley DC (2000) Structure of a covalently stabilized complex of a human alpha beta T-cell receptor, influenza HA peptide and MHC class II molecule, HLA-DR1. EMBO J 19:5611–5624
Hofmann K, Stoffel W (1993) Tmbase A database of membrane spanning proteins segments. Biol Chem Hoppe-Seyler 374:166
Inaba T, Koseki H, Suzuki M, Taniguchi M (1991) Double-step and inverse polymerase chain reaction for sensitive detection and cloning of T-cell receptor variable region sequences. Int Immunol 3:1053–1057
Kumar S, Tamura K, Jakobsen IB, Nei M (2001) MEGA2: molecular evolutionary genetics analysis software. Bioinformatics 17:1244–1245
Lewin HA (1996) Genetic organisation, polymorphism and function of the bovine major histocompatibility complex. In: Schook LB, Lamont SJ (eds) (1996) The major histocompatibility complex of domestic animal species. CRC Press, Boca Raton, pp 65–98
Liljedahl M, Kuwana T, Fung-Leung WP, Jackson MR, Peterson PA, Karlsson L (1996) HLA-DO is a lysosomal resident which requires association with HLA-DM for efficient intracellular transport. EMBO J 15:4817–4824
MacHugh ND, Mburu JK, Hamilton MJ, Davis WC (1998) Characterisation of a monoclonal antibody recognising the CD3epsilon chain of the cattle T-cell receptor complex. Vet Immunol Immunopathol 61:25–35
Madden DR (1995) The three-dimensional structure of peptide-MHC complexes. Annu Rev Immunol 13:587–622
Mann AJ, Abraham LJ, Cameron PU, Robinson W, Giphart MJ, Dawkins RL (1993) The caprine MHC contains DYA genes. Immunogenetics 37:292–295
McKeever DJ, MacHugh ND, Goddeeris BM, Awino E, Morrison WI (1991) Bovine afferent lymph veiled cells differ from blood monocytes in phenotype and accessory function. J Immunol 147:3703–3709
Niimi M, Nakai Y, Aida Y (1995) Nucleotide sequences and molecular evolution of the DMA and DMB genes of the bovine MHC. Biochem Biophys Res Commun 271:522–528
O’Callaghan CA, Bell JI (1998) Structure and function of the human MHC class Ib molecules HLA-E, HLA-F and HLA-G. Immunol Rev 163:129–138
Poel JJ van der, Groenen MEM, Dijkhof RJM, Ruyter D, Giphart MJ (1990) The nucleotide sequence of bovine MHC class II alpha genes: DRA, DQA and DYA. Immunogenetics 31:29–36
Quackenbush J, Cho J, Lee D, Liang F, Holt I, Karamycheva S, Parvizi B, Pertea G, Sultana R, White J (2001) The TIGR gene indices: analysis of gene transcript sequences in highly sampled eukaryotic species. Nucleic Acids Res 29:159–164
Reinherz EL, Tan K, Tang L, Kern P, Liu J, **ong Y, Hussey RE, Smolyar A, Hare B, Zhang R, Joachimiak A, Chang HC, Wagner G, Wang J (1999) The crystal structure of a T-cell receptor in complex with peptide and MHC class II. Science 286:1913–21
Stone RT, Muggli-Cockett NE (1990) Partial nucleotide sequence of a novel bovine major histocompatibility complex class II β-chain gene BoLA-DIB. Anim Genet 21:353–360
Stone RT, Muggli-Cockett NE (1993) BoLA-DIB: species distribution, linkage with DOB, and northern analysis. Anim Genet 24:41–45
Taxman DJ, Cressman DE, Ting JP-Y (2000) Identification of class II transcriptional activator-induced genes by representational difference analysis: discoordinate regulation of the DNα/DOβ heterodimer. J Immunol 165:1410–1416
Thompson JD, Higgins DG, Gibson TJ (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22:4673–4680
Totte P, Vachiery N, Martinez D, Trap I, Ballingall KT, MacHugh ND, Bensaid A, Werenne J (1996) Recombinant bovine interferon gamma inhibits the growth of Cowdria ruminantium but fails to induce major histocompatibility complex class II following infection of endothelial cells. Vet Immunol Immunopathol 53:61–71
Walter W, Scheuer C, Lingnau K, Reichert TE, Schmitt E, Loos M, Maeurer MJ (2000). H2-M, a facilitator of MHC class II peptide loading, and its negative modulator H2-O are differentially expressed in response to proinflammatory cytokines. Immunogenetics 51:794–804
Wang JH, Meijers R, **ong Y, Liu JH, Sakihama T, Zhang R, Joachimiak A, Reinherz EL (2001) Crystal structure of the human CD4 N-terminal two-domain fragment complexed to a class II MHC molecule. Proc Natl Acad Sci USA 98:10799–10804
Williams GW, Faller M (1999) PIX: a peptide identification system at the HGMP-RC. http://www.hgmp.mrc.ac.uk/Registered/Webapp/pix/
Woodgett JR, Gould KL, Hunter T (1986) Substrate specificity of protein kinase C. Use of synthetic peptides corresponding to physiological sites as probes for substrate recognition requirements. Eur J Biochem 161:177–184
Wright H (1995) Genes of the ovine major histocompatibility complex class II region. PhD thesis, University of Edinburgh
Wright H, Ballingall KT, Redmond J (1994) The DY sub-region of the sheep MHC contains an A/B gene pair. Immunogenetics 40:230–234
Wright H, Redmond J, Wright F, Ballingall KT (1995) The nucleotide sequence of the sheep MHC class II DNA gene. Immunogenetics 41:131–133
Wright H, Redmond J, Ballingall KT (1996) The sheep orthologue of the HLA-DOB gene. Immunogenetics 43:76–79
Yeager M, Hughes AL (1999) Evolution of the mammalian MHC: natural selection, recombination, and convergent evolution. Immunol Rev 167:45–58
Acknowledgements
The authors wish to thank Dr. Bernadette Dutia for providing the sheep class II-specific monoclonal antibodies, the Clinical Division of the Moredun Institute for providing samples and supporting cannulation studies and the Wellcome Trust Centre for Research in Comparative Respiratory Medicine for providing laboratory facilities. All experiments comply with the regulatory requirements of the United Kingdom. K. Ballingall acknowledges the funding support of the Wellcome Trust through grant 065442.
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Nucleotide sequence data reported here have the following accession numbers: AJ580583 and AJ580584
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Ballingall, K.T., Ellis, S.A., MacHugh, N.D. et al. The DY genes of the cattle MHC: expression and comparative analysis of an unusual class II MHC gene pair. Immunogenetics 55, 748–755 (2004). https://doi.org/10.1007/s00251-004-0641-x
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DOI: https://doi.org/10.1007/s00251-004-0641-x