Skip to main content
PMC home page
The EMBO Journal logoLink to The EMBO Journal
. 1988 Jun;7(6):1661–1668. doi: 10.1002/j.1460-2075.1988.tb02993.x

Complex rearrangements within the human J delta-C delta/J alpha-C alpha locus and aberrant recombination between J alpha segments.

R Baer 1, T Boehm 1, H Yssel 1, H Spits 1, T H Rabbitts 1
PMCID: PMC457150  PMID: 2971534

Abstract

We have examined DNA rearrangements within a 120 kb cloned region of the human T cell receptor J delta-C delta/J alpha-C alpha locus. Three types of pattern emerge from an analysis of T cell lines and clones. Firstly, cells with two rearrangements within J delta-C delta; secondly, cells with one rearrangement within J delta-C delta and one or more J alpha rearrangements, and finally, cells with rearrangements within J alpha and consequential deletion of the delta locus. Further analysis by cloning of rearrangements within the J alpha locus show that, in addition to V alpha-J alpha joins, J alpha-J alpha aberrant recombinations occur and rearrangement data indicate that such events are frequent. A model is presented to account for such recombinations.

Full text

PDF

Images in this article

1663Image
on p.1663
1663Image
on p.1663

Selected References

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

  1. Alarcon B., De Vries J., Pettey C., Boylston A., Yssel H., Terhorst C., Spits H. The T-cell receptor gamma chain-CD3 complex: implication in the cytotoxic activity of a CD3+ CD4- CD8- human natural killer clone. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3861–3865. doi: 10.1073/pnas.84.11.3861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baer R., Chen K. C., Smith S. D., Rabbitts T. H. Fusion of an immunoglobulin variable gene and a T cell receptor constant gene in the chromosome 14 inversion associated with T cell tumors. Cell. 1985 Dec;43(3 Pt 2):705–713. doi: 10.1016/0092-8674(85)90243-0. [DOI] [PubMed] [Google Scholar]
  3. Baer R., Forster A., Rabbitts T. H. The mechanism of chromosome 14 inversion in a human T cell lymphoma. Cell. 1987 Jul 3;50(1):97–105. doi: 10.1016/0092-8674(87)90666-0. [DOI] [PubMed] [Google Scholar]
  4. Baer R., Heppell A., Taylor A. M., Rabbitts P. H., Boullier B., Rabbitts T. H. The breakpoint of an inversion of chromosome 14 in a T-cell leukemia: sequences downstream of the immunoglobulin heavy chain locus are implicated in tumorigenesis. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9069–9073. doi: 10.1073/pnas.84.24.9069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Baer R., Lefranc M. P., Minowada J., Forster A., Stinson M. A., Rabbitts T. H. Organization of the T-cell receptor alpha-chain gene and rearrangement in human T-cell leukaemias. Mol Biol Med. 1986 Jun;3(3):265–277. [PubMed] [Google Scholar]
  6. Band H., Hochstenbach F., McLean J., Hata S., Krangel M. S., Brenner M. B. Immunochemical proof that a novel rearranging gene encodes the T cell receptor delta subunit. Science. 1987 Oct 30;238(4827):682–684. doi: 10.1126/science.3672118. [DOI] [PubMed] [Google Scholar]
  7. Bankier A. T., Weston K. M., Barrell B. G. Random cloning and sequencing by the M13/dideoxynucleotide chain termination method. Methods Enzymol. 1987;155:51–93. doi: 10.1016/0076-6879(87)55009-1. [DOI] [PubMed] [Google Scholar]
  8. Boehm T., Baer R., Lavenir I., Forster A., Waters J. J., Nacheva E., Rabbitts T. H. The mechanism of chromosomal translocation t(11;14) involving the T-cell receptor C delta locus on human chromosome 14q11 and a transcribed region of chromosome 11p15. EMBO J. 1988 Feb;7(2):385–394. doi: 10.1002/j.1460-2075.1988.tb02825.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bonyhadi M., Weiss A., Tucker P. W., Tigelaar R. E., Allison J. P. Delta is the Cx-gene product in the gamma/delta antigen receptor of dendritic epidermal cells. Nature. 1987 Dec 10;330(6148):574–576. doi: 10.1038/330574a0. [DOI] [PubMed] [Google Scholar]
  10. Born W., Miles C., White J., O'Brien R., Freed J. H., Marrack P., Kappler J., Kubo R. T. Peptide sequences of T-cell receptor delta and gamma chains are identical to predicted X and gamma proteins. Nature. 1987 Dec 10;330(6148):572–574. doi: 10.1038/330572a0. [DOI] [PubMed] [Google Scholar]
  11. Brenner M. B., McLean J., Scheft H., Riberdy J., Ang S. L., Seidman J. G., Devlin P., Krangel M. S. Two forms of the T-cell receptor gamma protein found on peripheral blood cytotoxic T lymphocytes. Nature. 1987 Feb 19;325(6106):689–694. doi: 10.1038/325689a0. [DOI] [PubMed] [Google Scholar]
  12. Chien Y. H., Iwashima M., Kaplan K. B., Elliott J. F., Davis M. M. A new T-cell receptor gene located within the alpha locus and expressed early in T-cell differentiation. 1987 Jun 25-Jul 1Nature. 327(6124):677–682. doi: 10.1038/327677a0. [DOI] [PubMed] [Google Scholar]
  13. Chien Y. H., Iwashima M., Wettstein D. A., Kaplan K. B., Elliott J. F., Born W., Davis M. M. T-cell receptor delta gene rearrangements in early thymocytes. Nature. 1987 Dec 24;330(6150):722–727. doi: 10.1038/330722a0. [DOI] [PubMed] [Google Scholar]
  14. Croce C. M., Isobe M., Palumbo A., Puck J., Ming J., Tweardy D., Erikson J., Davis M., Rovera G. Gene for alpha-chain of human T-cell receptor: location on chromosome 14 region involved in T-cell neoplasms. Science. 1985 Mar 1;227(4690):1044–1047. doi: 10.1126/science.3919442. [DOI] [PubMed] [Google Scholar]
  15. Durdik J., Moore M. W., Selsing E. Novel kappa light-chain gene rearrangements in mouse lambda light chain-producing B lymphocytes. Nature. 1984 Feb 23;307(5953):749–752. doi: 10.1038/307749a0. [DOI] [PubMed] [Google Scholar]
  16. Early P., Huang H., Davis M., Calame K., Hood L. An immunoglobulin heavy chain variable region gene is generated from three segments of DNA: VH, D and JH. Cell. 1980 Apr;19(4):981–992. doi: 10.1016/0092-8674(80)90089-6. [DOI] [PubMed] [Google Scholar]
  17. Hata S., Brenner M. B., Krangel M. S. Identification of putative human T cell receptor delta complementary DNA clones. Science. 1987 Oct 30;238(4827):678–682. doi: 10.1126/science.3499667. [DOI] [PubMed] [Google Scholar]
  18. Hayday A. C., Diamond D. J., Tanigawa G., Heilig J. S., Folsom V., Saito H., Tonegawa S. Unusual organization and diversity of T-cell receptor alpha-chain genes. 1985 Aug 29-Sep 4Nature. 316(6031):828–832. doi: 10.1038/316828a0. [DOI] [PubMed] [Google Scholar]
  19. Honjo T. Immunoglobulin genes. Annu Rev Immunol. 1983;1:499–528. doi: 10.1146/annurev.iy.01.040183.002435. [DOI] [PubMed] [Google Scholar]
  20. Huang C. C., Hou Y., Woods L. K., Moore G. E., Minowada J. Cytogenetic study of human lymphoid T-cell lines derived from lymphocytic leukemia. J Natl Cancer Inst. 1974 Sep;53(3):655–660. doi: 10.1093/jnci/53.3.655. [DOI] [PubMed] [Google Scholar]
  21. Höchtl J., Zachau H. G. A novel type of aberrant recombination in immunoglobulin genes and its implications for V-J joining mechanism. Nature. 1983 Mar 17;302(5905):260–263. doi: 10.1038/302260a0. [DOI] [PubMed] [Google Scholar]
  22. Karn J., Matthes H. W., Gait M. J., Brenner S. A new selective phage cloning vector, lambda 2001, with sites for XbaI, BamHI, HindIII, EcoRI, SstI and XhoI. Gene. 1984 Dec;32(1-2):217–224. doi: 10.1016/0378-1119(84)90049-0. [DOI] [PubMed] [Google Scholar]
  23. Kelley D. E., Wiedemann L. M., Pittet A. C., Strauss S., Nelson K. J., Davis J., Van Ness B., Perry R. P. Nonproductive kappa immunoglobulin genes: recombinational abnormalities and other lesions affecting transcription, RNA processing, turnover, and translation. Mol Cell Biol. 1985 Jul;5(7):1660–1675. doi: 10.1128/mcb.5.7.1660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kimura N., Toyonaga B., Yoshikai Y., Du R. P., Mak T. W. Sequences and repertoire of the human T cell receptor alpha and beta chain variable region genes in thymocytes. Eur J Immunol. 1987 Mar;17(3):375–383. doi: 10.1002/eji.1830170312. [DOI] [PubMed] [Google Scholar]
  25. Klein M. H., Concannon P., Everett M., Kim L. D., Hunkapiller T., Hood L. Diversity and structure of human T-cell receptor alpha-chain variable region genes. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6884–6888. doi: 10.1073/pnas.84.19.6884. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kleinfield R., Hardy R. R., Tarlinton D., Dangl J., Herzenberg L. A., Weigert M. Recombination between an expressed immunoglobulin heavy-chain gene and a germline variable gene segment in a Ly 1+ B-cell lymphoma. 1986 Aug 28-Sep 3Nature. 322(6082):843–846. doi: 10.1038/322843a0. [DOI] [PubMed] [Google Scholar]
  27. Koning F., Maloy W. L., Cohen D., Coligan J. E. Independent association of T cell receptor beta and gamma chains with CD3 in the same cell. J Exp Med. 1987 Aug 1;166(2):595–600. doi: 10.1084/jem.166.2.595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Le Beau M. M., McKeithan T. W., Shima E. A., Goldman-Leikin R. E., Chan S. J., Bell G. I., Rowley J. D., Diaz M. O. T-cell receptor alpha-chain gene is split in a human T-cell leukemia cell line with a t(11;14)(p15;q11). Proc Natl Acad Sci U S A. 1986 Dec;83(24):9744–9748. doi: 10.1073/pnas.83.24.9744. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. LeFranc M. P., Forster A., Baer R., Stinson M. A., Rabbitts T. H. Diversity and rearrangement of the human T cell rearranging gamma genes: nine germ-line variable genes belonging to two subgroups. Cell. 1986 Apr 25;45(2):237–246. doi: 10.1016/0092-8674(86)90388-0. [DOI] [PubMed] [Google Scholar]
  30. Lefranc M. P., Forster A., Rabbitts T. H. Genetic polymorphism and exon changes of the constant regions of the human T-cell rearranging gene gamma. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9596–9600. doi: 10.1073/pnas.83.24.9596. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Lefranc M. P., Rabbitts T. H. Two tandemly organized human genes encoding the T-cell gamma constant-region sequences show multiple rearrangement in different T-cell types. Nature. 1985 Aug 1;316(6027):464–466. doi: 10.1038/316464a0. [DOI] [PubMed] [Google Scholar]
  32. Leiden J. M., Fraser J. D., Strominger J. L. The complete primary structure of the T-cell receptor genes from an alloreactive cytotoxic human T-lymphocyte clone. Immunogenetics. 1986;24(1):17–23. doi: 10.1007/BF00372293. [DOI] [PubMed] [Google Scholar]
  33. Lindsten T., Fowlkes B. J., Samelson L. E., Davis M. M., Chien Y. H. Transient rearrangements of the T cell antigen receptor alpha locus in early thymocytes. J Exp Med. 1987 Sep 1;166(3):761–775. doi: 10.1084/jem.166.3.761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Loh E. Y., Lanier L. L., Turck C. W., Littman D. R., Davis M. M., Chien Y. H., Weiss A. Identification and sequence of a fourth human T cell antigen receptor chain. Nature. 1987 Dec 10;330(6148):569–572. doi: 10.1038/330569a0. [DOI] [PubMed] [Google Scholar]
  35. Mengle-Gaw L., Willard H. F., Smith C. I., Hammarström L., Fischer P., Sherrington P., Lucas G., Thompson P. W., Baer R., Rabbitts T. H. Human T-cell tumours containing chromosome 14 inversion or translocation with breakpoints proximal to immunoglobulin joining regions at 14q32. EMBO J. 1987 Aug;6(8):2273–2280. doi: 10.1002/j.1460-2075.1987.tb02501.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Quertermous T., Strauss W. M., Van Dongen J. J., Seidman J. G. Human T cell gamma chain joining regions and T cell development. J Immunol. 1987 Apr 15;138(8):2687–2690. [PubMed] [Google Scholar]
  37. Rabbitts T. H., Lefranc M. P., Stinson M. A., Sims J. E., Schroder J., Steinmetz M., Spurr N. L., Solomon E., Goodfellow P. N. The chromosomal location of T-cell receptor genes and a T cell rearranging gene: possible correlation with specific translocations in human T cell leukaemia. EMBO J. 1985 Jun;4(6):1461–1465. doi: 10.1002/j.1460-2075.1985.tb03803.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Reth M., Gehrmann P., Petrac E., Wiese P. A novel VH to VHDJH joining mechanism in heavy-chain-negative (null) pre-B cells results in heavy-chain production. 1986 Aug 28-Sep 3Nature. 322(6082):840–842. doi: 10.1038/322840a0. [DOI] [PubMed] [Google Scholar]
  39. Sakano H., Maki R., Kurosawa Y., Roeder W., Tonegawa S. Two types of somatic recombination are necessary for the generation of complete immunoglobulin heavy-chain genes. Nature. 1980 Aug 14;286(5774):676–683. doi: 10.1038/286676a0. [DOI] [PubMed] [Google Scholar]
  40. Sanger F., Coulson A. R., Barrell B. G., Smith A. J., Roe B. A. Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing. J Mol Biol. 1980 Oct 25;143(2):161–178. doi: 10.1016/0022-2836(80)90196-5. [DOI] [PubMed] [Google Scholar]
  41. Sangster R. N., Minowada J., Suciu-Foca N., Minden M., Mak T. W. Rearrangement and expression of the alpha, beta, and gamma chain T cell receptor genes in human thymic leukemia cells and functional T cells. J Exp Med. 1986 Jun 1;163(6):1491–1508. doi: 10.1084/jem.163.6.1491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Seidman J. G., Leder P. A mutant immunoglobulin light chain is formed by aberrant DNA- and RNA-splicing events. Nature. 1980 Aug 21;286(5775):779–783. doi: 10.1038/286779a0. [DOI] [PubMed] [Google Scholar]
  43. Sim G. K., Yagüe J., Nelson J., Marrack P., Palmer E., Augustin A., Kappler J. Primary structure of human T-cell receptor alpha-chain. Nature. 1984 Dec 20;312(5996):771–775. doi: 10.1038/312771a0. [DOI] [PubMed] [Google Scholar]
  44. Siminovitch K. A., Bakhshi A., Goldman P., Korsmeyer S. J. A uniform deleting element mediates the loss of kappa genes in human B cells. Nature. 1985 Jul 18;316(6025):260–262. doi: 10.1038/316260a0. [DOI] [PubMed] [Google Scholar]
  45. Sims J. E., Tunnacliffe A., Smith W. J., Rabbitts T. H. Complexity of human T-cell antigen receptor beta-chain constant- and variable-region genes. Nature. 1984 Dec 6;312(5994):541–545. doi: 10.1038/312541a0. [DOI] [PubMed] [Google Scholar]
  46. Staden R. The current status and portability of our sequence handling software. Nucleic Acids Res. 1986 Jan 10;14(1):217–231. doi: 10.1093/nar/14.1.217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Tighe L., Forster A., Clark D. M., Boylston A. W., Lavenir I., Rabbitts T. H. Unusual forms of T cell gamma mRNA in a human T cell leukemia cell line: implications for gamma gene expression. Eur J Immunol. 1987 Dec;17(12):1729–1736. doi: 10.1002/eji.1830171208. [DOI] [PubMed] [Google Scholar]
  48. Toyonaga B., Yoshikai Y., Vadasz V., Chin B., Mak T. W. Organization and sequences of the diversity, joining, and constant region genes of the human T-cell receptor beta chain. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8624–8628. doi: 10.1073/pnas.82.24.8624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Tunnacliffe A., Kefford R., Milstein C., Forster A., Rabbitts T. H. Sequence and evolution of the human T-cell antigen receptor beta-chain genes. Proc Natl Acad Sci U S A. 1985 Aug;82(15):5068–5072. doi: 10.1073/pnas.82.15.5068. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. 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]
  51. Vieira J., Messing J. The pUC plasmids, an M13mp7-derived system for insertion mutagenesis and sequencing with synthetic universal primers. Gene. 1982 Oct;19(3):259–268. doi: 10.1016/0378-1119(82)90015-4. [DOI] [PubMed] [Google Scholar]
  52. Winoto A., Mjolsness S., Hood L. Genomic organization of the genes encoding mouse T-cell receptor alpha-chain. 1985 Aug 29-Sep 4Nature. 316(6031):832–836. doi: 10.1038/316832a0. [DOI] [PubMed] [Google Scholar]
  53. Yoshikai Y., Clark S. P., Taylor S., Sohn U., Wilson B. I., Minden M. D., Mak T. W. Organization and sequences of the variable, joining and constant region genes of the human T-cell receptor alpha-chain. 1985 Aug 29-Sep 4Nature. 316(6031):837–840. doi: 10.1038/316837a0. [DOI] [PubMed] [Google Scholar]
  54. Yoshikai Y., Kimura N., Toyonaga B., Mak T. W. Sequences and repertoire of human T cell receptor alpha chain variable region genes in mature T lymphocytes. J Exp Med. 1986 Jul 1;164(1):90–103. doi: 10.1084/jem.164.1.90. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES