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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
. 1995 Dec 19;92(26):12105–12109. doi: 10.1073/pnas.92.26.12105

Cloning and comparative analysis of the human pre-T-cell receptor alpha-chain gene.

P Del Porto 1, L Bruno 1, M G Mattei 1, H von Boehmer 1, C Saint-Ruf 1
PMCID: PMC40305  PMID: 8618853

Abstract

In immature T cells the T-cell receptor (TCR) beta-chain gene is rearranged and expressed before the TCR alpha-chain gene. At this stage TCR beta chain can form disulfide-linked heterodimers with the pre-T-cell receptor alpha chain (pTalpha). Using the recently isolated murine pTalpha cDNA as a probe, we have isolated the human pTalpha cDNA. The complete nucleotide sequence predicts a mature protein of 282 aa consisting of an extracellular immunoglobulin-like domain, a connecting peptide, a transmembrane region, and a long cytoplasmic tail. Amino acid sequence comparison of human pTalpha with the mouse pTalpha molecule reveals high sequence homology in the extracellular as well as the transmembrane region. In contrast, the cytoplasmic region differs in amino acid composition and in length from the murine homologue. The human pTalpha gene is expressed in immature but not mature T cells and is located at the p21.2-p12 region of the short arm of chromosome 6.

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Selected References

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  1. Bentley G. A., Boulot G., Karjalainen K., Mariuzza R. A. Crystal structure of the beta chain of a T cell antigen receptor. Science. 1995 Mar 31;267(5206):1984–1987. doi: 10.1126/science.7701320. [DOI] [PubMed] [Google Scholar]
  2. Birnboim H. C., Doly J. A rapid alkaline extraction procedure for screening recombinant plasmid DNA. Nucleic Acids Res. 1979 Nov 24;7(6):1513–1523. doi: 10.1093/nar/7.6.1513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Casorati G., Traunecker A., Karjalainen K. The T cell receptor alpha beta V-J shuffling shows lack of autonomy between the combining site and the constant domain of the receptor chains. Eur J Immunol. 1993 Feb;23(2):586–589. doi: 10.1002/eji.1830230246. [DOI] [PubMed] [Google Scholar]
  4. Caspar-Bauguil S., Arnaud J., Huchenq A., Hein W. R., Geisler C., Rubin B. A highly conserved phenylalanine in the alpha, beta-T cell receptor (TCR) constant region determines the integrity of TCR/CD3 complexes. Scand J Immunol. 1994 Sep;40(3):323–336. doi: 10.1111/j.1365-3083.1994.tb03469.x. [DOI] [PubMed] [Google Scholar]
  5. Chang H. C., Moingeon P., Pedersen R., Lucich J., Stebbins C., Reinherz E. L. Involvement of the PPPGHR motif in T cell activation via CD2. J Exp Med. 1990 Jul 1;172(1):351–355. doi: 10.1084/jem.172.1.351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cosson P., Lankford S. P., Bonifacino J. S., Klausner R. D. Membrane protein association by potential intramembrane charge pairs. Nature. 1991 May 30;351(6325):414–416. doi: 10.1038/351414a0. [DOI] [PubMed] [Google Scholar]
  7. Fehling H. J., Krotkova A., Saint-Ruf C., von Boehmer H. Crucial role of the pre-T-cell receptor alpha gene in development of alpha beta but not gamma delta T cells. Nature. 1995 Jun 29;375(6534):795–798. doi: 10.1038/375795a0. [DOI] [PubMed] [Google Scholar]
  8. Fehling H. J., Laplace C., Mattei M. G., Saint-Ruf C., von Boehmer H. Genomic structure and chromosomal location of the mouse pre-T-cell receptor alpha gene. Immunogenetics. 1995;42(4):275–281. doi: 10.1007/BF00176445. [DOI] [PubMed] [Google Scholar]
  9. Frohman M. A., Dush M. K., Martin G. R. Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8998–9002. doi: 10.1073/pnas.85.23.8998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Galy A., Verma S., Bárcena A., Spits H. Precursors of CD3+CD4+CD8+ cells in the human thymus are defined by expression of CD34. Delineation of early events in human thymic development. J Exp Med. 1993 Aug 1;178(2):391–401. doi: 10.1084/jem.178.2.391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Geisler C., Rubin B., Caspar-Bauguil S., Champagne E., Vangsted A., Hou X., Gajhede M. Structural mutations of C-domains in members of the Ig superfamily. Consequences for the interactions between the T cell antigen receptor and the zeta 2 homodimer. J Immunol. 1992 Jun 1;148(11):3469–3477. [PubMed] [Google Scholar]
  12. Godfrey D. I., Zlotnik A. Control points in early T-cell development. Immunol Today. 1993 Nov;14(11):547–553. doi: 10.1016/0167-5699(93)90186-O. [DOI] [PubMed] [Google Scholar]
  13. Groettrup M., Baron A., Griffiths G., Palacios R., von Boehmer H. T cell receptor (TCR) beta chain homodimers on the surface of immature but not mature alpha, gamma, delta chain deficient T cell lines. EMBO J. 1992 Jul;11(7):2735–2745. doi: 10.1002/j.1460-2075.1992.tb05339.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Groettrup M., von Boehmer H. T cell receptor beta chain dimers on immature thymocytes from normal mice. Eur J Immunol. 1993 Jun;23(6):1393–1396. doi: 10.1002/eji.1830230633. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Kisielow P., von Boehmer H. Development and selection of T cells: facts and puzzles. Adv Immunol. 1995;58:87–209. doi: 10.1016/s0065-2776(08)60620-3. [DOI] [PubMed] [Google Scholar]
  17. Kraft D. L., Weissman I. L., Waller E. K. Differentiation of CD3-4-8- human fetal thymocytes in vivo: characterization of a CD3-4+8- intermediate. J Exp Med. 1993 Jul 1;178(1):265–277. doi: 10.1084/jem.178.1.265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Loh E. Y., Elliott J. F., Cwirla S., Lanier L. L., Davis M. M. Polymerase chain reaction with single-sided specificity: analysis of T cell receptor delta chain. Science. 1989 Jan 13;243(4888):217–220. doi: 10.1126/science.2463672. [DOI] [PubMed] [Google Scholar]
  19. Mattei M. G., Philip N., Passage E., Moisan J. P., Mandel J. L., Mattei J. F. DNA probe localization at 18p113 band by in situ hybridization and identification of a small supernumerary chromosome. Hum Genet. 1985;69(3):268–271. doi: 10.1007/BF00293038. [DOI] [PubMed] [Google Scholar]
  20. Melchers F., Karasuyama H., Haasner D., Bauer S., Kudo A., Sakaguchi N., Jameson B., Rolink A. The surrogate light chain in B-cell development. Immunol Today. 1993 Feb;14(2):60–68. doi: 10.1016/0167-5699(93)90060-X. [DOI] [PubMed] [Google Scholar]
  21. Nossal G. J. Negative selection of lymphocytes. Cell. 1994 Jan 28;76(2):229–239. doi: 10.1016/0092-8674(94)90331-x. [DOI] [PubMed] [Google Scholar]
  22. Ossendorp F., Jacobs H., van der Horst G., de Vries E., Berns A., Borst J. T cell receptor-alpha beta lacking the beta-chain V domain can be expressed at the cell surface but prohibits T cell maturation. J Immunol. 1992 Jun 15;148(12):3714–3722. [PubMed] [Google Scholar]
  23. Pearse M., Gallagher P., Wilson A., Wu L., Fisicaro N., Miller J. F., Scollay R., Shortman K. Molecular characterization of T-cell antigen receptor expression by subsets of CD4- CD8- murine thymocytes. Proc Natl Acad Sci U S A. 1988 Aug;85(16):6082–6086. doi: 10.1073/pnas.85.16.6082. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Pearson W. R., Lipman D. J. Improved tools for biological sequence comparison. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2444–2448. doi: 10.1073/pnas.85.8.2444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Raulet D. H., Garman R. D., Saito H., Tonegawa S. Developmental regulation of T-cell receptor gene expression. Nature. 1985 Mar 7;314(6006):103–107. doi: 10.1038/314103a0. [DOI] [PubMed] [Google Scholar]
  26. Saint-Ruf C., Ungewiss K., Groettrup M., Bruno L., Fehling H. J., von Boehmer H. Analysis and expression of a cloned pre-T cell receptor gene. Science. 1994 Nov 18;266(5188):1208–1212. doi: 10.1126/science.7973703. [DOI] [PubMed] [Google Scholar]
  27. Schibler U., Tosi M., Pittet A. C., Fabiani L., Wellauer P. K. Tissue-specific expression of mouse alpha-amylase genes. J Mol Biol. 1980 Sep 5;142(1):93–116. doi: 10.1016/0022-2836(80)90208-9. [DOI] [PubMed] [Google Scholar]
  28. Simon T., Rajewsky K. Antibody domain mutants demonstrate autonomy of the antigen binding site. EMBO J. 1990 Apr;9(4):1051–1056. doi: 10.1002/j.1460-2075.1990.tb08209.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Snodgrass H. R., Dembić Z., Steinmetz M., von Boehmer H. Expression of T-cell antigen receptor genes during fetal development in the thymus. Nature. 1985 May 16;315(6016):232–233. doi: 10.1038/315232a0. [DOI] [PubMed] [Google Scholar]
  30. Williams A. F., Barclay A. N. The immunoglobulin superfamily--domains for cell surface recognition. Annu Rev Immunol. 1988;6:381–405. doi: 10.1146/annurev.iy.06.040188.002121. [DOI] [PubMed] [Google Scholar]
  31. Yu H., Chen J. K., Feng S., Dalgarno D. C., Brauer A. W., Schreiber S. L. Structural basis for the binding of proline-rich peptides to SH3 domains. Cell. 1994 Mar 11;76(5):933–945. doi: 10.1016/0092-8674(94)90367-0. [DOI] [PubMed] [Google Scholar]
  32. von Boehmer H. Positive selection of lymphocytes. Cell. 1994 Jan 28;76(2):219–228. doi: 10.1016/0092-8674(94)90330-1. [DOI] [PubMed] [Google Scholar]

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