Abstract
The differentiation mechanisms that force thymocytes into the T-cell receptor (TCR)-alpha beta or TCR-gamma delta lineage are poorly understood, but rearrangement processes in the TCR-alpha/delta locus are likely to play an important role. It is assumed that the TCR-delta gene is deleted prior to V alpha-J alpha rearrangements by rearrangement of the so-called TCR-delta-deleting elements delta Rec and psi J alpha. However, the TCR-delta gene can also be deleted via V delta-J alpha rearrangements. We studied the different TCR-delta-deleting rearrangements of V delta 1, delta Rec, V delta 2 and V delta 3 to J alpha gene segments in human thymocytes and peripheral blood using polymerase chain reaction analysis. The V delta 1 gene segment is the most upstream V delta gene segment tested and appears to rearrange to almost all J alpha gene segments. In contrast, the delta Rec and V delta 2 gene segments only rearrange to the 5'-located J alpha gene segments, thereby preserving an extensive TCR-alpha combinatorial diversity, because most J alpha gene segments are kept available for subsequent V alpha-J alpha rearrangements. Based on our combined data we hypothesize that the different V delta gene segments and the delta Rec gene segment play different roles in T-cell development with regard to TCR-delta deletion.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Borst J., Wicherink A., Van Dongen J. J., De Vries E., Comans-Bitter W. M., Wassenaar F., Van Den Elsen P. Non-random expression of T cell receptor gamma and delta variable gene segments in functional T lymphocyte clones from human peripheral blood. Eur J Immunol. 1989 Sep;19(9):1559–1568. doi: 10.1002/eji.1830190907. [DOI] [PubMed] [Google Scholar]
- Breit T. M., Van Dongen J. J. Unravelling human T-cell receptor junctional region sequences. Thymus. 1994;22(3):177–199. [PubMed] [Google Scholar]
- Breit T. M., Wolvers-Tettero I. L., Beishuizen A., Verhoeven M. A., van Wering E. R., van Dongen J. J. Southern blot patterns, frequencies, and junctional diversity of T-cell receptor-delta gene rearrangements in acute lymphoblastic leukemia. Blood. 1993 Nov 15;82(10):3063–3074. [PubMed] [Google Scholar]
- Breit T. M., Wolvers-Tettero I. L., Bogers A. J., de Krijger R. R., Wladimiroff J. W., van Dongen J. J. Rearrangements of the human TCRD-deleting elements. Immunogenetics. 1994;40(1):70–75. doi: 10.1007/BF00163967. [DOI] [PubMed] [Google Scholar]
- Breit T. M., Wolvers-Tettero I. L., Hählen K., van Wering E. R., van Dongen J. J. Extensive junctional diversity of gamma delta T-cell receptors expressed by T-cell acute lymphoblastic leukemias: implications for the detection of minimal residual disease. Leukemia. 1991 Dec;5(12):1076–1086. [PubMed] [Google Scholar]
- Giachino C., Rocci M. P., Bottaro M., Matullo G., De Libero G., Migone N. T cell receptor V delta 2-C alpha transcripts are present in the thymus but virtually absent in the periphery. J Immunol. 1994 Aug 15;153(4):1637–1644. [PubMed] [Google Scholar]
- Hansen-Hagge T. E., Mahotka C., Panzer-Grümayer R. E., Reuter H. J., Schwarz K., van Dongen J. J., Bartram C. R. Alternative splicing restricts translation of rearrangements at the T-cell receptor delta/alpha locus. Blood. 1995 Apr 1;85(7):1888–1896. [PubMed] [Google Scholar]
- Hockett R. D., Jr, Nuñez G., Korsmeyer S. J. Evolutionary comparison of murine and human delta T-cell receptor deleting elements. New Biol. 1989 Dec;1(3):266–274. [PubMed] [Google Scholar]
- Koop B. F., Rowen L., Wang K., Kuo C. L., Seto D., Lenstra J. A., Howard S., Shan W., Deshpande P., Hood L. The human T-cell receptor TCRAC/TCRDC (C alpha/C delta) region: organization, sequence, and evolution of 97.6 kb of DNA. Genomics. 1994 Feb;19(3):478–493. doi: 10.1006/geno.1994.1097. [DOI] [PubMed] [Google Scholar]
- Miossec C., Caignard A., Ferradini L., Roman-Roman S., Faure F., Michalaki H., Triebel F., Hercend T. Molecular characterization of human T cell receptor alpha chains including a V delta 1-encoded variable segment. Eur J Immunol. 1991 Apr;21(4):1061–1064. doi: 10.1002/eji.1830210430. [DOI] [PubMed] [Google Scholar]
- Moss P. A., Rosenberg W. M., Zintzaras E., Bell J. I. Characterization of the human T cell receptor alpha-chain repertoire and demonstration of a genetic influence on V alpha usage. Eur J Immunol. 1993 May;23(5):1153–1159. doi: 10.1002/eji.1830230526. [DOI] [PubMed] [Google Scholar]
- Peyrat M. A., Davodeau F., Houde I., Romagné F., Necker A., Leget C., Cervoni J. P., Cerf-Bensussan N., Vié H., Bonneville M. Repertoire analysis of human peripheral blood lymphocytes using a human V delta 3 region-specific monoclonal antibody. Characterization of dual T cell receptor (TCR) delta-chain expressors and alpha beta T cells expressing V delta 3J alpha C alpha-encoded TCR chains. J Immunol. 1995 Sep 15;155(6):3060–3067. [PubMed] [Google Scholar]
- Satyanarayana K., Hata S., Devlin P., Roncarolo M. G., De Vries J. E., Spits H., Strominger J. L., Krangel M. S. Genomic organization of the human T-cell antigen-receptor alpha/delta locus. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8166–8170. doi: 10.1073/pnas.85.21.8166. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sottini A., Imberti L., Fiordalisi G., Primi D. Use of variable human V delta genes to create functional T cell receptor alpha chain transcripts. Eur J Immunol. 1991 Oct;21(10):2455–2459. doi: 10.1002/eji.1830211023. [DOI] [PubMed] [Google Scholar]
- Verschuren M. C., Wolvers-Tettero I. L., Breit T. M., Noordzij J., van Wering E. R., van Dongen J. J. Preferential rearrangements of the T cell receptor-delta-deleting elements in human T cells. J Immunol. 1997 Feb 1;158(3):1208–1216. [PubMed] [Google Scholar]
- Verschuren M. C., van Bergen C. J., van Gastel-Mol E. J., Bogers A. J., van Dongen J. J. A DNA binding protein in human thymocytes recognizes the T cell receptor-delta-deleting element psi J alpha. J Immunol. 1996 May 15;156(10):3806–3814. [PubMed] [Google Scholar]
- Villey I., Caillol D., Selz F., Ferrier P., de Villartay J. P. Defect in rearrangement of the most 5' TCR-J alpha following targeted deletion of T early alpha (TEA): implications for TCR alpha locus accessibility. Immunity. 1996 Oct;5(4):331–342. doi: 10.1016/s1074-7613(00)80259-9. [DOI] [PubMed] [Google Scholar]
- Wucherpfennig K. W., Liao Y. J., Prendergast M., Prendergast J., Hafler D. A., Strominger J. L. Human fetal liver gamma/delta T cells predominantly use unusual rearrangements of the T cell receptor delta and gamma loci expressed on both CD4+CD8- and CD4-CD8- gamma/delta T cells. J Exp Med. 1993 Feb 1;177(2):425–432. doi: 10.1084/jem.177.2.425. [DOI] [PMC free article] [PubMed] [Google Scholar]
- de Chasseval R., de Villartay J. P. Functional characterization of the promoter for the human germ-line T cell receptor J alpha (TEA) transcript. Eur J Immunol. 1993 Jun;23(6):1294–1298. doi: 10.1002/eji.1830230616. [DOI] [PubMed] [Google Scholar]
- de Villartay J. P., Hockett R. D., Coran D., Korsmeyer S. J., Cohen D. I. Deletion of the human T-cell receptor delta-gene by a site-specific recombination. Nature. 1988 Sep 8;335(6186):170–174. doi: 10.1038/335170a0. [DOI] [PubMed] [Google Scholar]
- de Villartay J. P., Lewis D., Hockett R., Waldmann T. A., Korsmeyer S. J., Cohen D. I. Deletional rearrangement in the human T-cell receptor alpha-chain locus. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8608–8612. doi: 10.1073/pnas.84.23.8608. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van Dongen J. J., Comans-Bitter W. M., Wolvers-Tettero I. L., Borst J. Development of human T lymphocytes and their thymus-dependency. Thymus. 1990 Nov-Dec;16(3-4):207–234. [PubMed] [Google Scholar]
- van Dongen J. J., Wolvers-Tettero I. L. Analysis of immunoglobulin and T cell receptor genes. Part I: Basic and technical aspects. Clin Chim Acta. 1991 Apr;198(1-2):1–91. doi: 10.1016/0009-8981(91)90246-9. [DOI] [PubMed] [Google Scholar]
- van der Stoep N., de Krijger R., Bruining J., Koning F., van den Elsen P. Analysis of early fetal T-cell receptor delta chain in humans. Immunogenetics. 1990;32(5):331–336. doi: 10.1007/BF00211647. [DOI] [PubMed] [Google Scholar]