Abstract
To understand the biology of γδ T cells in ruminants, it is necessary to have a comprehensive picture of γδ T-cell receptor gene diversity and expression. In this study, three new subgroups of bovine T-cell receptor δ (TRD) variable genes were identified by RT-PCR and sequencing and homology with TRDV genes from other mammals determined. Previously unidentified TRDV subgroup genes described in this study include the bovine homologues of ovine TRDV2, TRDV3, and TRDV4 which were named accordingly. TRDV2 subgroup has two genes (TRDV2-1 and TRDV2-2) while we found the previously identified TRDV1 has at least eight genes corresponding to separate genomic sequences. Nucleotide and amino acid sequences for particular gene subgroups between cattle and sheep were more than 87% identical but identities among TRDV subgroups within a species were much less, with bovine TRDV4 having <45% identity to the other three bovine TRDV gene subgroups. Analysis of circulating bovine γδ T cells revealed that genes from all four TRDV subgroups were expressed in combination with TRDJ1, TRDJ3, and TRDC, although TRDV4 was the least represented, and all displayed a variety of CDR3 junctional lengths. Finally, some genes within the TRDV1, TRDV2, and TRDV3 subgroups recombined with TRAV incorporating TRAJs, suggesting dual use.
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References
Allison TJ, Garboczi DN (2002) Structure of γδ T cell receptors and their recognition of non-peptide antigens. Mol Immunol 38:1051–1061
Blumerman SL, Herzig CTA, Rogers AN, Telfer JC, Baldwin CL (2006) Differential TCR gene usage between WC1– and WC1+ ruminant γσ T cell subpopulations including those responding to bacterial antigen DOI: 10.1007/s00251-006-0122-5
Bukowski JF, Morita CT, Tanaka Y, Bloom BR, Brenner MB, Band H (1995) Vγ2Vδ2 TCR-dependent recognition of non-peptide antigens and Daudi cells analyzed by TCR gene transfer. J Immunol 154:998–1006
Chen ZW (2002) Comparative biology of γδ T cells. Sci Prog 85:347–358
Chenna R, Sugawara H, Koike T, Lopez R, Gibson TJ, Higgins DG, Thompson JD (2003) Multiple sequence alignment with the Clustal series of programs. Nucleic Acids Res 31:3497–3500
Chien YH, Jores R, Crowley MP (1996) Recognition by γ/δ T cells. Annu Rev Immunol 14:511–532
Clark SP, Arden B, Kabelitz D, Mak TW (1995) Comparison of human and mouse T-cell receptor variable gene segment subfamilies. Immunogenetics 42:531–540
Cooper MD, Chen CL, Bucy RP, Thompson CB (1991) Avian T cell ontogeny. Adv Immunol 50:87–117
Crews S, Griffin J, Huang H, Calame K, Hood L (1981) A single VH gene segment encodes the immune response to phosphorylcholine: somatic mutation is correlated with the class of the antibody. Cell 25:59–66
Daubenberger CA, Taracha EL, Gaidulis L, Davis WC, McKeever DJ (1999) Bovine γδ T-cell responses to the intracellular protozoan parasite Theileria parva. Infect Immun 67:2241–2249
Davis MM, Chien YH (2003) T-cell antigen receptors. In: Paul WE (ed) Fundamental Immunology, 5th edn. Williams & Wilkins, Philadelphia, PA
Egan PJ, Carding SR (2000) Downmodulation of the inflammatory response to bacterial infection by γδ T cells cytotoxic for activated macrophages. J Exp Med 191:2145–2158
Evans PS, Enders PJ, Yin C, Ruckwardt TJ, Malkovsky M, Pauza CD (2001) In vitro stimulation with a non-peptidic alkylphosphate expands cells expressing Vγ2-Jγ1.2/Vδ2 T-cell receptors. Immunology 104:19–27
Glusman G, Rowen L, Lee I, Boysen C, Roach JC, Smit AF, Wang K, Koop BF, Hood L (2001) Comparative genomics of the human and mouse T cell receptor loci. Immunity 15:337–349
Groh V, Steinle A, Bauer S, Spies T (1998) Recognition of stress-induced MHC molecules by intestinal epithelial γδ T cells. Science 279:1737–1740
Halsey WA Jr, Palmer BE, DeMartini JC, Howell MD (1999) Analysis of sheep T-cell receptor β-chain heterogeneity. Immunogenetics 49:206–214
Havran WL, Chien YH, Allison JP (1991) Recognition of self antigens by skin-derived T cells with invariant γδ antigen receptors. Science 252:1430–1432
Hayday AC (2000) γδ Cells: a right time and a right place for a conserved third way of protection. Annu Rev Immunol 18:975–1026
Hein WR, Dudler L (1993) Divergent evolution of T cell repertoires: extensive diversity and developmentally regulated expression of the sheep γδ T cell receptor. EMBO J 12:715–724
Hein WR, Dudler L (1997) TCR γδ+ cells are prominent in normal bovine skin and express a diverse repertoire of antigen receptors. Immunology 91:58–64
Hein WR, Mackay CR (1991) Prominence of γδ T cells in the ruminant immune system. Immunol Today 12:30–34
Herzig C, Blumerman S, Lefranc MP, Baldwin C (2006) Bovine T cell receptor gamma variable and constant genes: combinatorial usage by circulating γδ T cells. Immunogenetics 58:138–151
Lahmers KK, Norimine J, Abrahamsen MS, Palmer GH, Brown WC (2005) The CD4+ T cell immunodominant Anaplasma marginale major surface protein 2 stimulates γδ T cell clones that express unique T cell receptors. J Leukoc Biol 77:199–208
Lefranc MP, Lefranc G (2001) The T cell receptor FactsBook. Academic, London, UK, pp 398
Lefranc MP, Pommie C, Ruiz M, Giudicelli V, Foulquier E, Truong L, Thouvenin-Contet V, Lefranc G (2003) IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains. Dev Comp Immunol 27:55–77
Massari S, Antonacci R, Lanave C, Ciccarese S (2000) Genomic organization of sheep TRDJ segments and their expression in the δ-chain repertoire in thymus. Immunogenetics 52:1–8
Miccoli MC, Antonacci R, Vaccarelli G, Lanave C, Massari S, Cribiu EP, Ciccarese S (2003) Evolution of TRG clusters in cattle and sheep genomes as drawn from the structural analysis of the ovine TRG2@ locus. J Mol Evol 57:52–62
Morita CT, Parker CM, Brenner MB, Band H (1994) TCR usage and functional capabilities of human γδ T cells at birth. J Immunol 153:3979–3988
Naiman BM, Alt D, Bolin CA, Zuerner R, Baldwin CL (2001) Protective killed Leptospira borgpetersenii vaccine induces potent Th1 immunity comprising responses by CD4 and γδ T lymphocytes. Infect Immun 69:7550–7558
Nishimura H, Hirokawa M, Fujishima N, Fujishima M, Miura I, Sawada K (2004) Contribution of complementarity-determining region 3 of the T-cell receptor Vδ2 chain to the recognition of aminobisphosphonates by human γδ T-cells. Int J Hematol 79:369–376
Okragly AJ, Hanby-Flarida M, Mann D, Baldwin CL (1996) Bovine γ/δ T-cell proliferation is associated with self-derived molecules constitutively expressed in vivo on mononuclear phagocytes. Immunology 87:71–79
Ota Y, Kobata T, Seki M, Yagita H, Shimada S, Huang YY, Takagaki Y, Okumura K (1992) Extrathymic origin of Vγ1/Vδ6 T cells in the skin. Eur J Immunol 22:595–598
Parker CM, Groh V, Band H, Porcelli SA, Morita C, Fabbi M, Glass D, Strominger JL, Brenner MB (1990) Evidence for extrathymic changes in the T cell receptor γ/δ repertoire. J Exp Med 171:1597–1612
Pfeffer K, Schoel B, Gulle H, Kaufmann SH, Wagner H (1990) Primary responses of human T cells to mycobacteria: a frequent set of γδ T cells are stimulated by protease-resistant ligands. Eur J Immunol 20:1175–1179
Rogers AN, Vanburen DG, Hedblom EE, Tilahun ME, Telfer JC, Baldwin CL (2005) γδ T cell function varies with the expressed WC1 coreceptor. J Immunol 174:3386–3393
Sathiyaseelan T, Naiman B, Welte S, Machugh N, Black SJ, Baldwin CL (2002) Immunological characterization of a γδ T-cell stimulatory ligand on autologous monocytes. Immunology 105:181–189
Shen Y, Zhou D, Qiu L, Lai X, Simon M, Shen L, Kou Z, Wang Q, Jiang L, Estep J, Hunt R, Clagett M, Sehgal PK, Li Y, Zeng X, Morita CT, Brenner MB, Letvin NL, Chen ZW (2002) Adaptive immune response of Vγ2Vδ2+ T cells during mycobacterial infections. Science 295:2255–2258
Shin S, El Diwany R, Schaffert S, Adams EJ, Garcia KC, Pereira P, Chien YH (2005) Antigen recognition determinants of γδ T cell receptors. Science 308:252–255
Steele CR, Oppenheim DE, Hayday AC (2000) γδ T cells: non-classical ligands for non-classical cells. Curr Biol 10:R282–R285
Su C, Jakobsen I, Gu X, Nei M (1999) Diversity and evolution of T-cell receptor variable region genes in mammals and birds. Immunogenetics 50:301–308
Weber-Arden J, Wilbert OM, Kabelitz D, Arden B (2000) Vδ repertoire during thymic ontogeny suggests three novel waves of γδ TCR expression. J Immunol 164:1002–1012
Welsh MD, Kennedy HE, Smyth AJ, Girvin RM, Andersen P, Pollock JM (2002) Responses of bovine WC1+ γδ T cells to protein and nonprotein antigens of Mycobacterium bovis. Infect Immun 70:6114–6120
Yamashita S, Tanaka Y, Harazaki M, Mikami B, Minato N (2003) Recognition mechanism of non-peptide antigens by human γδ T cells. Int Immunol 15:1301–1307
Acknowledgements
This work was supported by the National Research Initiative of the USDA CSREES, grant #2002-02038 and 2004-01157, and the Massachusetts Agricultural Experiment Station Project No. MAS00851. Dr. Marie-Paule Lefranc is gratefully acknowledged for her assistance in gaining approval for the names of new bovine genes and Dr. Janice Telfer for the advice in quantitation of PCR products.
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The nucleotide sequence data reported are available in the DDBJ/EMBL/GenBank database under the accession numbers DQ275147, DQ275148, DQ275149, and DQ280318.
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Herzig, C.T.A., Blumerman, S.L. & Baldwin, C.L. Identification of three new bovine T-cell receptor delta variable gene subgroups expressed by peripheral blood T cells. Immunogenetics 58, 746–757 (2006). https://doi.org/10.1007/s00251-006-0136-z
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DOI: https://doi.org/10.1007/s00251-006-0136-z