Abstract
T cells play important regulatory roles in the immune responses of vertebrates. Antigen-specific T-cell activation involves T-cell receptor (TCR) recognition of a peptide antigen presented by a major histocompatibility complex molecule, and much has been learned about this antigen-recognition process through structural and genetic studies of mammalian TCRs. Although previous studies have demonstrated that avian T cells express cell-surface molecules analogous to the mammalian TCR heterodimers, TCR genes have not been identified in nonmammalian species. We now report the cloning of a cDNA that encodes the beta chain of the chicken TCR. Southern blot analysis using this TCR beta cDNA probe demonstrated that the chicken TCR beta locus was clonally rear-ranged in chicken T-cell lines. TCR beta mRNA was expressed in cells isolated from the thymus but not in cells from the bursa of Fabricius where B cells are generated. Sequence analysis of six additional TCR beta cDNAs suggested the existence of at least two variable (V) region families, three joining (J) elements, and single diversity (D) and constant (C) elements. As in mammals, considerable nucleotide diversity was observed at the junctions of the variable, diversity, and joining elements in chicken TCR beta cDNAs. Genomic V beta and J beta elements were also cloned and sequenced. Both elements are flanked by classical heptamer/nonamer recombination signal sequences. Although the chicken and mammalian TCR beta chains displayed only 31% overall amino acid sequence identity, a number of conserved structural features were observed. These data indicate that (i) the chicken TCR beta repertoire is generated by combinatorial and junctional diversity and (ii) despite divergent evolution at the level of nucleotide sequence, important structural features of the TCR beta polypeptide are conserved between avian and mammalian species.
Full text
PDF![7856](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b7/54849/d618116adbed/pnas01045-0067.png)
![7857](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b7/54849/9b48340e4c2e/pnas01045-0068.png)
![7858](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b7/54849/0a875d044318/pnas01045-0069.png)
![7859](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b7/54849/00de7820d7eb/pnas01045-0070.png)
![7860](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b7/54849/3beb3a5993ce/pnas01045-0071.png)
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alcover A., Mariuzza R. A., Ermonval M., Acuto O. Lysine 271 in the transmembrane domain of the T-cell antigen receptor beta chain is necessary for its assembly with the CD3 complex but not for alpha/beta dimerization. J Biol Chem. 1990 Mar 5;265(7):4131–4135. [PubMed] [Google Scholar]
- Anderson S. J., Chou H. S., Loh D. Y. A conserved sequence in the T-cell receptor beta-chain promoter region. Proc Natl Acad Sci U S A. 1988 May;85(10):3551–3554. doi: 10.1073/pnas.85.10.3551. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Bougueleret L., Claverie J. M. Variability analysis of the human and mouse T-cell receptor beta chains. Immunogenetics. 1987;26(4-5):304–308. doi: 10.1007/BF00346527. [DOI] [PubMed] [Google Scholar]
- Calnek B. W., Shek W. R., Schat K. A. Spontaneous and induced herpesvirus genome expression in Marek's disease tumor cell lines. Infect Immun. 1981 Nov;34(2):483–491. doi: 10.1128/iai.34.2.483-491.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Chan M. M., Chen C. L., Ager L. L., Cooper M. D. Identification of the avian homologues of mammalian CD4 and CD8 antigens. J Immunol. 1988 Apr 1;140(7):2133–2138. [PubMed] [Google Scholar]
- Chen C. L., Ager L. L., Gartland G. L., Cooper M. D. Identification of a T3/T cell receptor complex in chickens. J Exp Med. 1986 Jul 1;164(1):375–380. doi: 10.1084/jem.164.1.375. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen C. L., Cihak J., Lösch U., Cooper M. D. Differential expression of two T cell receptors, TcR1 and TcR2, on chicken lymphocytes. Eur J Immunol. 1988 Apr;18(4):539–543. doi: 10.1002/eji.1830180408. [DOI] [PubMed] [Google Scholar]
- Chien Y. H., Gascoigne N. R., Kavaler J., Lee N. E., Davis M. M. Somatic recombination in a murine T-cell receptor gene. Nature. 1984 May 24;309(5966):322–326. doi: 10.1038/309322a0. [DOI] [PubMed] [Google Scholar]
- Clevers H., Alarcon B., Wileman T., Terhorst C. The T cell receptor/CD3 complex: a dynamic protein ensemble. Annu Rev Immunol. 1988;6:629–662. doi: 10.1146/annurev.iy.06.040188.003213. [DOI] [PubMed] [Google Scholar]
- Cohn M. The T-cell receptor mediating restrictive recognition of antigen. Cell. 1983 Jul;33(3):657–669. doi: 10.1016/0092-8674(83)90009-0. [DOI] [PubMed] [Google Scholar]
- Cooper M. D., Raymond D. A., Peterson R. D., South M. A., Good R. A. The functions of the thymus system and the bursa system in the chicken. J Exp Med. 1966 Jan 1;123(1):75–102. doi: 10.1084/jem.123.1.75. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Dembić Z., Haas W., Weiss S., McCubrey J., Kiefer H., von Boehmer H., Steinmetz M. Transfer of specificity by murine alpha and beta T-cell receptor genes. Nature. 1986 Mar 20;320(6059):232–238. doi: 10.1038/320232a0. [DOI] [PubMed] [Google Scholar]
- Gascoigne N. R., Chien Y., Becker D. M., Kavaler J., Davis M. M. Genomic organization and sequence of T-cell receptor beta-chain constant- and joining-region genes. Nature. 1984 Aug 2;310(5976):387–391. doi: 10.1038/310387a0. [DOI] [PubMed] [Google Scholar]
- Hedrick S. M., Nielsen E. A., Kavaler J., Cohen D. I., Davis M. M. Sequence relationships between putative T-cell receptor polypeptides and immunoglobulins. Nature. 1984 Mar 8;308(5955):153–158. doi: 10.1038/308153a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Leiden J. M., Strominger J. L. Generation of diversity of the beta chain of the human T-lymphocyte receptor for antigen. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4456–4460. doi: 10.1073/pnas.83.12.4456. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Petryniak B., Staudt L. M., Postema C. E., McCormack W. T., Thompson C. B. Characterization of chicken octamer-binding proteins demonstrates that POU domain-containing homeobox transcription factors have been highly conserved during vertebrate evolution. Proc Natl Acad Sci U S A. 1990 Feb;87(3):1099–1103. doi: 10.1073/pnas.87.3.1099. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Raulet D. H. The structure, function, and molecular genetics of the gamma/delta T cell receptor. Annu Rev Immunol. 1989;7:175–207. doi: 10.1146/annurev.iy.07.040189.001135. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Saito H., Kranz D. M., Takagaki Y., Hayday A. C., Eisen H. N., Tonegawa S. Complete primary structure of a heterodimeric T-cell receptor deduced from cDNA sequences. 1984 Jun 28-Jul 4Nature. 309(5971):757–762. doi: 10.1038/309757a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Siu G., Clark S. P., Yoshikai Y., Malissen M., Yanagi Y., Strauss E., Mak T. W., Hood L. The human T cell antigen receptor is encoded by variable, diversity, and joining gene segments that rearrange to generate a complete V gene. Cell. 1984 Jun;37(2):393–401. doi: 10.1016/0092-8674(84)90369-6. [DOI] [PubMed] [Google Scholar]
- 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]
- Sowder J. T., Chen C. L., Ager L. L., Chan M. M., Cooper M. D. A large subpopulation of avian T cells express a homologue of the mammalian T gamma/delta receptor. J Exp Med. 1988 Feb 1;167(2):315–322. doi: 10.1084/jem.167.2.315. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thompson C. B., Humphries E. H., Carlson L. M., Chen C. L., Neiman P. E. The effect of alterations in myc gene expression on B cell development in the bursa of Fabricius. Cell. 1987 Nov 6;51(3):371–381. doi: 10.1016/0092-8674(87)90633-7. [DOI] [PubMed] [Google Scholar]
- Vainio O., Veromaa T., Eerola E., Toivanen P., Ratcliffe M. J. Antigen-presenting cell-T cell interaction in the chicken is MHC class II antigen restricted. J Immunol. 1988 May 1;140(9):2864–2868. [PubMed] [Google Scholar]
- Watson D. K., McWilliams M. J., Papas T. S. A unique amino-terminal sequence predicted for the chicken proto-ets protein. Virology. 1988 Nov;167(1):1–7. doi: 10.1016/0042-6822(88)90047-5. [DOI] [PubMed] [Google Scholar]
- Yoshikai Y., Anatoniou D., Clark S. P., Yanagi Y., Sangster R., Van den Elsen P., Terhorst C., Mak T. W. Sequence and expression of transcripts of the human T-cell receptor beta-chain genes. Nature. 1984 Dec 6;312(5994):521–524. doi: 10.1038/312521a0. [DOI] [PubMed] [Google Scholar]
- 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]