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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Sep 1;88(17):7699–7703. doi: 10.1073/pnas.88.17.7699

Chicken T-cell receptor beta-chain diversity: an evolutionarily conserved D beta-encoded glycine turn within the hypervariable CDR3 domain.

W T McCormack 1, L W Tjoelker 1, G Stella 1, C E Postema 1, C B Thompson 1
PMCID: PMC52369  PMID: 1652759

Abstract

Unlike mammals, chickens generate an immunoglobulin (Ig) repertoire by a developmentally regulated process of intrachromosomal gene conversion, which results in nucleotide substitutions throughout the variable regions of the Ig heavy- and light-chain genes. In contrast to chicken Ig genes, we show in this report that diversity of the rearranged chicken T-cell receptor (TCR) beta-chain gene is generated by junctional heterogeneity, as observed in rearranged mammalian TCR genes. This junctional diversity increases during chicken development as a result of an increasing base-pair addition at the V beta-D beta and D beta-J beta joints (where V, D, and J are the variable, diversity, and joining gene segments). Despite the junctional hypervariability, however, almost all functional V beta-D beta-J beta junctions appear to encode a glycine-containing beta-turn. Such a turn may serve to position the amino acid side chains of a hypervariable TCR beta-chain loop with respect to the antigen-binding groove of the major histocompatibility complex molecule. Consistent with this hypothesis, the germ-line D beta nucleotide sequences of chickens, mice, rabbits, and humans have been highly conserved and encode a glycine in all three reading frames.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alt F. W., Baltimore D. Joining of immunoglobulin heavy chain gene segments: implications from a chromosome with evidence of three D-JH fusions. Proc Natl Acad Sci U S A. 1982 Jul;79(13):4118–4122. doi: 10.1073/pnas.79.13.4118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alt F. W., Blackwell T. K., DePinho R. A., Reth M. G., Yancopoulos G. D. Regulation of genome rearrangement events during lymphocyte differentiation. Immunol Rev. 1986 Feb;89:5–30. doi: 10.1111/j.1600-065x.1986.tb01470.x. [DOI] [PubMed] [Google Scholar]
  3. Asarnow D. M., Kuziel W. A., Bonyhadi M., Tigelaar R. E., Tucker P. W., Allison J. P. Limited diversity of gamma delta antigen receptor genes of Thy-1+ dendritic epidermal cells. Cell. 1988 Dec 2;55(5):837–847. doi: 10.1016/0092-8674(88)90139-0. [DOI] [PubMed] [Google Scholar]
  4. Barth R. K., Kim B. S., Lan N. C., Hunkapiller T., Sobieck N., Winoto A., Gershenfeld H., Okada C., Hansburg D., Weissman I. L. The murine T-cell receptor uses a limited repertoire of expressed V beta gene segments. Nature. 1985 Aug 8;316(6028):517–523. doi: 10.1038/316517a0. [DOI] [PubMed] [Google Scholar]
  5. Blackman M. A., Kappler J. W., Marrack P. T-cell specificity and repertoire. Immunol Rev. 1988 Jan;101:5–19. doi: 10.1111/j.1600-065x.1988.tb00730.x. [DOI] [PubMed] [Google Scholar]
  6. Carlson L. M., McCormack W. T., Postema C. E., Humphries E. H., Thompson C. B. Templated insertions in the rearranged chicken IgL V gene segment arise by intrachromosomal gene conversion. Genes Dev. 1990 Apr;4(4):536–547. doi: 10.1101/gad.4.4.536. [DOI] [PubMed] [Google Scholar]
  7. Chou P. Y., Fasman G. D. Beta-turns in proteins. J Mol Biol. 1977 Sep 15;115(2):135–175. doi: 10.1016/0022-2836(77)90094-8. [DOI] [PubMed] [Google Scholar]
  8. Clark S. P., Yoshikai Y., Taylor S., Siu G., Hood L., Mak T. W. Identification of a diversity segment of human T-cell receptor beta-chain, and comparison with the analogous murine element. 1984 Sep 27-Oct 3Nature. 311(5984):387–389. doi: 10.1038/311387a0. [DOI] [PubMed] [Google Scholar]
  9. Claverie J. M., Prochnicka-Chalufour A., Bougueleret L. Implications of a Fab-like structure for the T-cell receptor. Immunol Today. 1989 Jan;10(1):10–14. doi: 10.1016/0167-5699(89)90058-3. [DOI] [PubMed] [Google Scholar]
  10. Concannon P., Pickering L. A., Kung P., Hood L. Diversity and structure of human T-cell receptor beta-chain variable region genes. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6598–6602. doi: 10.1073/pnas.83.17.6598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cooper M. D., Chen C. L., Bucy R. P., Thompson C. B. Avian T cell ontogeny. Adv Immunol. 1991;50:87–117. doi: 10.1016/s0065-2776(08)60823-8. [DOI] [PubMed] [Google Scholar]
  12. Davis M. M., Bjorkman P. J. T-cell antigen receptor genes and T-cell recognition. Nature. 1988 Aug 4;334(6181):395–402. doi: 10.1038/334395a0. [DOI] [PubMed] [Google Scholar]
  13. Desiderio S. V., Yancopoulos G. D., Paskind M., Thomas E., Boss M. A., Landau N., Alt F. W., Baltimore D. Insertion of N regions into heavy-chain genes is correlated with expression of terminal deoxytransferase in B cells. Nature. 1984 Oct 25;311(5988):752–755. doi: 10.1038/311752a0. [DOI] [PubMed] [Google Scholar]
  14. Elliott J. F., Rock E. P., Patten P. A., Davis M. M., Chien Y. H. The adult T-cell receptor delta-chain is diverse and distinct from that of fetal thymocytes. Nature. 1988 Feb 18;331(6157):627–631. doi: 10.1038/331627a0. [DOI] [PubMed] [Google Scholar]
  15. Feeney A. J. Lack of N regions in fetal and neonatal mouse immunoglobulin V-D-J junctional sequences. J Exp Med. 1990 Nov 1;172(5):1377–1390. doi: 10.1084/jem.172.5.1377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Goverman J., Minard K., Shastri N., Hunkapiller T., Hansburg D., Sercarz E., Hood L. Rearranged beta T cell receptor genes in a helper T cell clone specific for lysozyme: no correlation between V beta and MHC restriction. Cell. 1985 Apr;40(4):859–867. doi: 10.1016/0092-8674(85)90345-9. [DOI] [PubMed] [Google Scholar]
  17. Gregoire K. E., Goldschneider I., Barton R. W., Bollum F. J. Ontogeny of terminal deoxynucleotidyl transferase-positive cells in lymphohemopoietic tissues of rat and mouse. J Immunol. 1979 Sep;123(3):1347–1352. [PubMed] [Google Scholar]
  18. Gu H., Förster I., Rajewsky K. Sequence homologies, N sequence insertion and JH gene utilization in VHDJH joining: implications for the joining mechanism and the ontogenetic timing of Ly1 B cell and B-CLL progenitor generation. EMBO J. 1990 Jul;9(7):2133–2140. doi: 10.1002/j.1460-2075.1990.tb07382.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hunkapiller T., Hood L. Diversity of the immunoglobulin gene superfamily. Adv Immunol. 1989;44:1–63. doi: 10.1016/s0065-2776(08)60639-2. [DOI] [PubMed] [Google Scholar]
  20. Ichihara Y., Hayashida H., Miyazawa S., Kurosawa Y. Only DFL16, DSP2, and DQ52 gene families exist in mouse immunoglobulin heavy chain diversity gene loci, of which DFL16 and DSP2 originate from the same primordial DH gene. Eur J Immunol. 1989 Oct;19(10):1849–1854. doi: 10.1002/eji.1830191014. [DOI] [PubMed] [Google Scholar]
  21. Kavaler J., Davis M. M., Chien Y. Localization of a T-cell receptor diversity-region element. Nature. 1984 Aug 2;310(5976):421–423. doi: 10.1038/310421a0. [DOI] [PubMed] [Google Scholar]
  22. Krangel M. S., Yssel H., Brocklehurst C., Spits H. A distinct wave of human T cell receptor gamma/delta lymphocytes in the early fetal thymus: evidence for controlled gene rearrangement and cytokine production. J Exp Med. 1990 Sep 1;172(3):847–859. doi: 10.1084/jem.172.3.847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lafaille J. J., DeCloux A., Bonneville M., Takagaki Y., Tonegawa S. Junctional sequences of T cell receptor gamma delta genes: implications for gamma delta T cell lineages and for a novel intermediate of V-(D)-J joining. Cell. 1989 Dec 1;59(5):859–870. doi: 10.1016/0092-8674(89)90609-0. [DOI] [PubMed] [Google Scholar]
  24. Leszczynski J. F., Rose G. D. Loops in globular proteins: a novel category of secondary structure. Science. 1986 Nov 14;234(4778):849–855. doi: 10.1126/science.3775366. [DOI] [PubMed] [Google Scholar]
  25. Loh E. Y., Cwirla S., Serafini A. T., Phillips J. H., Lanier L. L. Human T-cell-receptor delta chain: genomic organization, diversity, and expression in populations of cells. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9714–9718. doi: 10.1073/pnas.85.24.9714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. McCormack W. T., Thompson C. B. Chicken IgL variable region gene conversions display pseudogene donor preference and 5' to 3' polarity. Genes Dev. 1990 Apr;4(4):548–558. doi: 10.1101/gad.4.4.548. [DOI] [PubMed] [Google Scholar]
  27. McCormack W. T., Tjoelker L. W., Barth C. F., Carlson L. M., Petryniak B., Humphries E. H., Thompson C. B. Selection for B cells with productive IgL gene rearrangements occurs in the bursa of Fabricius during chicken embryonic development. Genes Dev. 1989 Jun;3(6):838–847. doi: 10.1101/gad.3.6.838. [DOI] [PubMed] [Google Scholar]
  28. McCormack W. T., Tjoelker L. W., Carlson L. M., Petryniak B., Barth C. F., Humphries E. H., Thompson C. B. Chicken IgL gene rearrangement involves deletion of a circular episome and addition of single nonrandom nucleotides to both coding segments. Cell. 1989 Mar 10;56(5):785–791. doi: 10.1016/0092-8674(89)90683-1. [DOI] [PubMed] [Google Scholar]
  29. Meek K. Analysis of junctional diversity during B lymphocyte development. Science. 1990 Nov 9;250(4982):820–823. doi: 10.1126/science.2237433. [DOI] [PubMed] [Google Scholar]
  30. Reynaud C. A., Anquez V., Dahan A., Weill J. C. A single rearrangement event generates most of the chicken immunoglobulin light chain diversity. Cell. 1985 Feb;40(2):283–291. doi: 10.1016/0092-8674(85)90142-4. [DOI] [PubMed] [Google Scholar]
  31. Reynaud C. A., Anquez V., Grimal H., Weill J. C. A hyperconversion mechanism generates the chicken light chain preimmune repertoire. Cell. 1987 Feb 13;48(3):379–388. doi: 10.1016/0092-8674(87)90189-9. [DOI] [PubMed] [Google Scholar]
  32. Reynaud C. A., Dahan A., Anquez V., Weill J. C. Somatic hyperconversion diversifies the single Vh gene of the chicken with a high incidence in the D region. Cell. 1989 Oct 6;59(1):171–183. doi: 10.1016/0092-8674(89)90879-9. [DOI] [PubMed] [Google Scholar]
  33. Rothenberg E., Triglia D. Clonal proliferation unlinked to terminal deoxynucleotidyl transferase synthesis in thymocytes of young mice. J Immunol. 1983 Apr;130(4):1627–1633. [PubMed] [Google Scholar]
  34. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  35. Sakano H., Kurosawa Y., Weigert M., Tonegawa S. Identification and nucleotide sequence of a diversity DNA segment (D) of immunoglobulin heavy-chain genes. Nature. 1981 Apr 16;290(5807):562–565. doi: 10.1038/290562a0. [DOI] [PubMed] [Google Scholar]
  36. Schiffer M., Wu T. T., Kabat E. A. Subgroups of variable region genes of beta chains of T-cell receptors for antigen. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4461–4463. doi: 10.1073/pnas.83.12.4461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Sibanda B. L., Thornton J. M. Beta-hairpin families in globular proteins. Nature. 1985 Jul 11;316(6024):170–174. doi: 10.1038/316170a0. [DOI] [PubMed] [Google Scholar]
  38. Siu G., Kronenberg M., Strauss E., Haars R., Mak T. W., Hood L. The structure, rearrangement and expression of D beta gene segments of the murine T-cell antigen receptor. 1984 Sep 27-Oct 3Nature. 311(5984):344–350. doi: 10.1038/311344a0. [DOI] [PubMed] [Google Scholar]
  39. Tjoelker L. W., Carlson L. M., Lee K., Lahti J., McCormack W. T., Leiden J. M., Chen C. L., Cooper M. D., Thompson C. B. Evolutionary conservation of antigen recognition: the chicken T-cell receptor beta chain. Proc Natl Acad Sci U S A. 1990 Oct;87(20):7856–7860. doi: 10.1073/pnas.87.20.7856. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Tunnacliffe A., Rabbitts T. H. Sequence of the D beta 2-J beta 2 region of the human T-cell receptor beta-chain locus. Nucleic Acids Res. 1985 Sep 25;13(18):6651–6661. doi: 10.1093/nar/13.18.6651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. von Boehmer H., Karjalainen K., Pelkonen J., Borgulya P., Rammensee H. G. The T-cell receptor for antigen in T-cell development and repertoire selection. Immunol Rev. 1988 Jan;101:21–37. doi: 10.1111/j.1600-065x.1988.tb00731.x. [DOI] [PubMed] [Google Scholar]

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