delta chain t cell antigen receptor gene rearrangement


Summary: Ordered rearrangement of T-cell variable gene regions coding for the delta-chain of antigen receptors.

Top Publications

  1. Liyanage M, Weaver Z, Barlow C, Coleman A, Pankratz D, Anderson S, et al. Abnormal rearrangement within the alpha/delta T-cell receptor locus in lymphomas from Atm-deficient mice. Blood. 2000;96:1940-6 pubmed
    ..The mechanisms that lead to tumorigenesis may be due to the involvement of ATM in monitoring double-stranded DNA breaks. (Blood. 2000;96:1940-1946) ..
  2. Krangel M, Carabana J, Abbarategui I, Schlimgen R, Hawwari A. Enforcing order within a complex locus: current perspectives on the control of V(D)J recombination at the murine T-cell receptor alpha/delta locus. Immunol Rev. 2004;200:224-32 pubmed
    ..We provide here a current view of cis-acting mechanisms that enforce the TCRalpha/delta locus developmental program, and we emphasize the unresolved issues that command the attention of our and other laboratories. ..
  3. Wilson A, de Villartay J, MacDonald H. T cell receptor delta gene rearrangement and T early alpha (TEA) expression in immature alpha beta lineage thymocytes: implications for alpha beta/gamma delta lineage commitment. Immunity. 1996;4:37-45 pubmed
    ..Finally, VDJ delta rearrangements in immature alpha beta cells appear to be random, supporting models in which alpha beta lineage commitment is determined independently of the rearrangement status at the TCR delta locus. ..
  4. Sleckman B, Bardon C, Ferrini R, Davidson L, Alt F. Function of the TCR alpha enhancer in alphabeta and gammadelta T cells. Immunity. 1997;7:505-15 pubmed
    ..Our findings imply that E alpha function is not limited to the TCR alpha components of the TCRalpha/delta locus or to the alpha beta lineage; rather, E alpha function is important in both alphabeta and gammadelta lineage T cells. ..
  5. Nakajima P, Menetski J, Roth D, Gellert M, Bosma M. V-D-J rearrangements at the T cell receptor delta locus in mouse thymocytes of the alpha beta lineage. Immunity. 1995;3:609-21 pubmed
    ..Thus, contrary to earlier proposals, commitment to the alpha beta lineage does not require recombinational silencing of the delta locus or its deletion by a site-specific mechanism prior to V alpha-J alpha rearrangement. ..
  6. Gallagher M, Obeid P, Marche P, Jouvin Marche E. Both TCR alpha and TCR delta chain diversity are regulated during thymic ontogeny. J Immunol. 2001;167:1447-53 pubmed
    ..Control of these waves appears to be linked directly to the ADV segments and their local chromatin environment, which may change over the course of T cell differentiation. ..
  7. Rytkönen Nissinen M, Hurwitz J, Pelkonen S, Levelt C, Pelkonen J. Early activation of TCR alpha gene rearrangement in fetal thymocytes. Eur J Immunol. 1999;29:2288-96 pubmed
    ..In addition, Vdelta1 Ddelta2 J alpha50 gene segments are replaced by secondary alpha rearrangements, indicating that thymocytes with the early alpha rearrangement are committed to the alphabeta lineage. ..
  8. Itohara S, Mombaerts P, Lafaille J, Iacomini J, Nelson A, Clarke A, et al. T cell receptor delta gene mutant mice: independent generation of alpha beta T cells and programmed rearrangements of gamma delta TCR genes. Cell. 1993;72:337-48 pubmed
  9. Hernandez Munain C, Lauzurica P, Krangel M. Regulation of T cell receptor delta gene rearrangement by c-Myb. J Exp Med. 1996;183:289-93 pubmed
    ..We demonstrate that an intact Myb binding site is necessary for efficient rearrangement of the minilocus substrate, suggesting that c-Myb plays a crucial role in activating VDJ recombination at the endogenous TCR-delta locus. ..

More Information


  1. Aude Garcia C, Gallagher M, Marche P, Jouvin Marche E. Preferential ADV-AJ association during recombination in the mouse T-cell receptor alpha/delta locus. Immunogenetics. 2001;52:224-30 pubmed
    ..Taken together, our results indicate that, in addition to the progressive opening of the ADV and AJ loci, the chromosomal location of ADV and AJ genes is a factor affecting AJ use in BALB/c mice. ..
  2. Jouvin Marche E, Aude Garcia C, Candeias S, Borel E, Hachemi Rachedi S, Gahéry Ségard H, et al. Differential chronology of TCRADV2 gene use by alpha and delta chains of the mouse TCR. Eur J Immunol. 1998;28:818-27 pubmed
    ..These results support independent control of TCRA and TCRD gene assembly. ..
  3. Pereira P, Hermitte V, Lembezat M, Boucontet L, Azuara V, Grigoriadou K. Developmentally regulated and lineage-specific rearrangement of T cell receptor Valpha/delta gene segments. Eur J Immunol. 2000;30:1988-97 pubmed
  4. Monroe R, Sleckman B, Monroe B, Khor B, Claypool S, Ferrini R, et al. Developmental regulation of TCR delta locus accessibility and expression by the TCR delta enhancer. Immunity. 1999;10:503-13 pubmed
    ..We conclude that E delta has an important role in TCR delta locus regulation at early, but not late, stages of gammadelta T cell development. ..
  5. Andre S, Kerfourn F, Affaticati P, Guerci A, Ravassard P, Fellah J. Highly restricted diversity of TCR delta chains of the amphibian Mexican axolotl (Ambystoma mexicanum) in peripheral tissues. Eur J Immunol. 2007;37:1621-33 pubmed
    ..Gene expression analysis showed the importance of the gut in T cell development. ..
  6. Nirmala K, Rajalekshmy K, Raman S, Shanta V, Rajkumar T. PCR-heteroduplex analysis of TCR gamma, delta and TAL-1 deletions in T-acute lymphoblastic leukemias: implications in the detection of minimal residual disease. Leuk Res. 2002;26:335-43 pubmed
    ..Thus, we conclude that PCR followed by HD analysis is a useful technique to monitor MRD in remission/relapse samples in ALL patients. ..
  7. Ghosh J, Romanow W, Murre C. Induction of a diverse T cell receptor gamma/delta repertoire by the helix-loop-helix proteins E2A and HEB in nonlymphoid cells. J Exp Med. 2001;193:769-76 pubmed
    ..These data indicate that a distinct but diverse TCR repertoire can be induced in nonlymphoid cells by the mere presence of the V(D)J recombinase and the transcriptional regulators, E2A and HEB. ..
  8. Toubai T, Tanaka J, Ota S, Fukuhara T, Hashino S, Kondo T, et al. Minimal residual disease (MRD) monitoring using rearrangement of T-cell receptor and immunoglobulin H gene in the treatment of adult acute lymphoblastic leukemia patients. Am J Hematol. 2005;80:181-7 pubmed
    ..013). A lower MRD in BM value after induction chemotherapy was associated significantly with longer survival in the log-rank test. Our data provide evidence that molecular MRD status of BM is a strong predictor of outcome in adult ALL. ..
  9. Huang C, Sleckman B. Developmental stage-specific regulation of TCR-alpha-chain gene assembly by intrinsic features of the TEA promoter. J Immunol. 2007;179:449-54 pubmed
  10. Krejci O, Prouzova Z, Horvath O, Trka J, Hrusak O. Cutting edge: TCR delta gene is frequently rearranged in adult B lymphocytes. J Immunol. 2003;171:524-7 pubmed
  11. Martinet L, Jean C, Dietrich G, Fournie J, Poupot R. PGE2 inhibits natural killer and gamma delta T cell cytotoxicity triggered by NKR and TCR through a cAMP-mediated PKA type I-dependent signaling. Biochem Pharmacol. 2010;80:838-45 pubmed publisher
    ..In the discussion, we focused on how these data should impact particular approaches in the treatment of cancer...
  12. Zhu C, Roth D. Characterization of coding ends in thymocytes of scid mice: implications for the mechanism of V(D)J recombination. Immunity. 1995;2:101-12 pubmed
    ..In scid/+ or wild-type thymocytes, hairpin coding ends are at least 1000-fold less abundant than signal ends. These results provide insight into the mechanism of V(D)J recombination. ..
  13. Specchia G, Liso A, Pannunzio A, Albano F, Mestice A, Pastore D, et al. Molecular detection of minimal residual disease is associated with early relapse in adult acute lymphoblastic leukemia. Haematologica. 2004;89:1271-3 pubmed
    ..In our experience, evaluation of MRD in adult ALL can help to identify high risk patients. ..
  14. Asnafi V, Beldjord K, Garand R, Millien C, Bahloul M, LeTutour P, et al. IgH DJ rearrangements within T-ALL correlate with cCD79a expression, an immature/TCRgammadelta phenotype and absence of IL7Ralpha/CD127 expression. Leukemia. 2004;18:1997-2001 pubmed
    ..gammadelta/IM lineage T-ALLs potentially include two distinct categories: predominantly IgH+, cCD79a+, CD127- cases which retain gammadelta and B lymphoid potential and IgH-, cCD79a-, CD127+ cases with restricted T lineage potential. ..
  15. Khor B, Wehrly T, Sleckman B. Chromosomal excision of TCRdelta chain genes is dispensable for alphabeta T cell lineage commitment. Int Immunol. 2005;17:225-32 pubmed
    ..However, alphabeta T cell development appears unperturbed in TCRalpha/delta(I/I) mice. Thus, excision of TCRdelta genes from the chromosome per se is not required for commitment of developing lymphocytes to the alphabeta T cell lineage. ..
  16. Przybylski G, Wanzeck J, Verschuren M, van Dongen J, Serke S, Schmidt C. Identification of a new cluster of T-cell receptor delta recombining elements. Immunology. 2003;108:16-23 pubmed
    ..We hypothesize, that in a similar manner to the classical deltaRec rearrangements, the deltaRec2 rearrangements might also contribute to T-cell differentiation towards the TCR-alphabeta lineage. ..
  17. Fronkova E, Krejci O, Kalina T, Horvath O, Trka J, Hrusak O. Lymphoid differentiation pathways can be traced by TCR delta rearrangements. J Immunol. 2005;175:2495-500 pubmed
    ..This contradicts recent challenges to the concept of separate lymphoid and myeloid differentiation. ..
  18. Couedel C, Lippert E, Bernardeau K, Bonneville M, Davodeau F. Allelic exclusion at the TCR delta locus and commitment to gamma delta lineage: different modalities apply to distinct human gamma delta subsets. J Immunol. 2004;172:5544-52 pubmed
    ..We propose that these distinct behaviors are related to the developmental stage at which rearrangements occur, as suggested by the patterns of accessibility to recombination sites that characterize the V delta 1 and V delta 2 subsets. ..
  19. Hawwari A, Krangel M. Regulation of TCR delta and alpha repertoires by local and long-distance control of variable gene segment chromatin structure. J Exp Med. 2005;202:467-72 pubmed
  20. Stagno F, Guglielmo P, Lo Nigro L, Santonocito A, Giustolisi R. T cell receptor delta-chain gene rearrangement in a novel case of adult NK cell leukemia. Acta Haematol. 2004;111:225-7 pubmed
    ..We here report the characteristics of a peculiar case of NK-cell acute leukemia with unusual agranular morphology and rearrangement of the T-cell receptor (TCR) delta-chain gene. ..
  21. Valetto A, Di Martino D, Scuderi F, Lanza T, Lanciotti M, Bottini F, et al. Detection of T cell receptor delta gene rearrangements in childhood B and T lineage acute lymphoblastic leukaemia by southern blot and PCR: technical comparison of two methods of analysis. Clin Lab Haematol. 2000;22:263-9 pubmed
    ..Two different types of rearrangements were chiefly detected: Vdelta2Ddelta3 and Ddelta2Ddelta3. In T-ALL patients, the predominant rearrangement involved the Vdelta1 and the Jdelta1 gene segments. ..
  22. Blanchong C, Olshefski R, Kahwash S. Large granular lymphocyte leukemia: case report of chronic neutropenia and rheumatoid arthritis-like symptoms in a child. Pediatr Dev Pathol. 2001;4:94-9 pubmed
    ..Although rare, large granular lymphocyte leukemia should be included in the differential diagnosis of chronic neutropenia in children. ..
  23. Hara H, Kishihara K, Matsuzaki G, Takimoto H, Tsukiyama T, Tigelaar R, et al. Development of dendritic epidermal T cells with a skewed diversity of gamma delta TCRs in V delta 1-deficient mice. J Immunol. 2000;165:3695-705 pubmed
  24. Kienker L, Ghosh M, Tucker P. Regulatory elements in the promoter of a murine TCRD V gene segment. J Immunol. 1998;161:791-804 pubmed
    ..Further, the possibility remains that the GATA and E box sites function in enhancer independent DV101S1 germline transcription. ..
  25. Kalataradi H, Eyster C, Fry A, Vollmer M, Fu Y, Born W, et al. Allelic differences in TCR gamma-chains alter gamma delta T cell antigen reactivity. J Immunol. 1994;153:1455-65 pubmed
    ..We propose that amino acid differences among those encoded by the AKR V gamma 1-J gamma 4-C gamma 4 gene are responsible for the lack of response, and reduce the ability of the TCR-gamma delta to bind the relevant Ag. ..
  26. Zha S, Bassing C, Sanda T, Brush J, Patel H, Goff P, et al. ATM-deficient thymic lymphoma is associated with aberrant tcrd rearrangement and gene amplification. J Exp Med. 2010;207:1369-80 pubmed publisher
    ..Overall, our studies reveal previously unexpected mechanisms that contribute to the oncogenic transformation of ATM-deficient T lineage cells. ..
  27. Joachims M, Chain J, Hooker S, Knott Craig C, Thompson L. Human alpha beta and gamma delta thymocyte development: TCR gene rearrangements, intracellular TCR beta expression, and gamma delta developmental potential--differences between men and mice. J Immunol. 2006;176:1543-52 pubmed
    ..Aspects that differ from the mouse are the status of TCR gene rearrangements at the nonexpressed loci, the timing of beta selection, and maintenance of gammadelta potential through the early double positive stage of development. ..
  28. Mittal S, Milner B, Johnston P, Culligan D. A case of hepatosplenic gamma-delta T-cell lymphoma with a transient response to fludarabine and alemtuzumab. Eur J Haematol. 2006;76:531-4 pubmed
    ..Given the dreadful prognosis with conventional chemotherapy, it is a regimen worth pursuing as a disease reduction strategy prior to allograft where appropriate. ..
  29. Fujishima N, Hirokawa M, Fujishima M, Wada C, Toyoshima I, Watanabe S, et al. Oligoclonal T cell expansion in blood but not in the thymus from a patient with thymoma-associated pure red cell aplasia. Haematologica. 2006;91:ECR47 pubmed
    ..Oligoclonal expansion of Vdelta1-expressing T cells remained unchanged after thymectomy. Thymus may not be the site of clonal T cell expansion in thymoma-associated PRCA. ..
  30. Stewart C, Walzer T, Robbins S, Malissen B, Vivier E, Prinz I. Germ-line and rearranged Tcrd transcription distinguish bona fide NK cells and NK-like gammadelta T cells. Eur J Immunol. 2007;37:1442-52 pubmed
    ..Instead, it ascribes chronic TCRgammadelta engagement as a means of acquiring NK-like function. ..
  31. Aplan P, Lombardi D, Reaman G, Sather H, Hammond G, Kirsch I. Involvement of the putative hematopoietic transcription factor SCL in T-cell acute lymphoblastic leukemia. Blood. 1992;79:1327-33 pubmed
    ..The resultant inappropriate expression of this putative transcription factor may then contribute to leukemic transformation in T-cell ALL. ..
  32. Yao L, Chen Z, Cen J, Liang J, Feng Y, He J, et al. The pattern of clonal immunoglobulin and T-cell receptor (Ig/TCR) gene rearrangements in Chinese adult acute lymphoblastic leukemia patients. Leuk Res. 2008;32:1735-40 pubmed publisher
    ..These results are useful for further MRD-RQ-PCR detection and quantification for all patients. ..
  33. Kreutzman A, Juvonen V, Kairisto V, Ekblom M, Stenke L, Seggewiss R, et al. Mono/oligoclonal T and NK cells are common in chronic myeloid leukemia patients at diagnosis and expand during dasatinib therapy. Blood. 2010;116:772-82 pubmed publisher
    ..The functional importance of clonal lymphocytes as a part of leukemia immune surveillance and the putative anergy-reversing role of dasatinib require further evaluation...
  34. Oyoshi M, Nagata H, Kimura N, Zhang Y, Demachi A, Hara T, et al. Preferential expansion of Vgamma9-JgammaP/Vdelta2-Jdelta3 gammadelta T cells in nasal T-cell lymphoma and chronic active Epstein-Barr virus infection. Am J Pathol. 2003;162:1629-38 pubmed
    ..The close association of EBV with this particular gammadelta T-cell population may provide a key to the etiology of EBV-positive lymphoproliferative diseases. ..
  35. Narazaki H, Watari E, Shimizu M, Owaki A, Das H, Fukunaga Y, et al. Perforin-dependent killing of tumor cells by Vgamma1Vdelta1-bearing T-cells. Immunol Lett. 2003;86:113-9 pubmed
    ..Thus, these results raise the possibility that some Vgamma1Vdelta1(+) T-cells could potentially be stimulated and lyse tumor cells via ligation of TCR/CD3-unassociated molecules. ..
  36. Dieli F, Ivanyi J, Marsh P, Williams A, Naylor I, Sireci G, et al. Characterization of lung gamma delta T cells following intranasal infection with Mycobacterium bovis bacillus Calmette-Guérin. J Immunol. 2003;170:463-9 pubmed
  37. Par G, Rukavina D, Podack E, Horanyi M, Szekeres Bartho J, Hegedûs G, et al. Decrease in CD3-negative-CD8dim(+) and Vdelta2/Vgamma9 TcR+ peripheral blood lymphocyte counts, low perforin expression and the impairment of natural killer cell activity is associated with chronic hepatitis C virus infection. J Hepatol. 2002;37:514-22 pubmed
  38. Poccia F, Cipriani B, Vendetti S, Colizzi V, Poquet Y, Battistini L, et al. CD94/NKG2 inhibitory receptor complex modulates both anti-viral and anti-tumoral responses of polyclonal phosphoantigen-reactive V gamma 9V delta 2 T lymphocytes. J Immunol. 1997;159:6009-17 pubmed
    ..The Vgamma9Vdelta2 T cell regulation through the CD94 receptor may be important for the potentially dual function in innate immunity, i.e., 1) NK-like and 2) TCR ligand-induced cytolytic activities. ..
  39. Chen B, Cui X, Sempowski G, Gooding M, Liu C, Haynes B, et al. A comparison of murine T-cell-depleted adult bone marrow and full-term fetal blood cells in hematopoietic engraftment and immune reconstitution. Blood. 2002;99:364-71 pubmed
    ..These results suggest that full-term fetal blood can engraft allogeneic hosts across the major histocompatibility barrier with slower hematopoietic engraftment and impaired immune reconstitution. ..
  40. van der Velden V, Szczepanski T, Wijkhuijs J, Hart P, Hoogeveen P, Hop W, et al. Age-related patterns of immunoglobulin and T-cell receptor gene rearrangements in precursor-B-ALL: implications for detection of minimal residual disease. Leukemia. 2003;17:1834-44 pubmed
  41. Sempowski G, Hale L, Sundy J, Massey J, Koup R, Douek D, et al. Leukemia inhibitory factor, oncostatin M, IL-6, and stem cell factor mRNA expression in human thymus increases with age and is associated with thymic atrophy. J Immunol. 2000;164:2180-7 pubmed
    ..p. to mice over 3 days induced thymic atrophy with loss of CD4+, CD8+ cortical thymocytes. Taken together, these data suggest a role for thymic cytokines in the process of thymic atrophy. ..
  42. Przybylski G, Oettle H, Siegert W, Schmidt C. Novel T-cell receptor delta gene rearrangement involving a recombining element located 2.6 kb 3' from the Vdelta2 gene segment. Leuk Res. 2001;25:1059-65 pubmed
    ..It may potentially lead to deletion of the deltaRec2(Ddelta)Jdelta1 complex and either to direct joining of a Vdelta region to one of the downstream Jdelta regions or to a rearrangement of the TCRalpha gene. ..
  43. Saito T, Togitani K, Murakami J, Watanabe T, Tanosaki R, Kobayashi Y, et al. Granular lymphocytic leukemia derived from gamma delta T-cell expressing cytotoxic molecules. Leuk Res. 2001;25:259-61 pubmed
    ..CT scan showed splenomegaly but no lymph node enlargement. A diagnosis of gamma delta T-GLL was made, and she has been followed up without any therapies for more than 4 years. ..
  44. Leduc I, Hempel W, Mathieu N, Verthuy C, Bouvier G, Watrin F, et al. T cell development in TCR beta enhancer-deleted mice: implications for alpha beta T cell lineage commitment and differentiation. J Immunol. 2000;165:1364-73 pubmed
    ..We discuss these data with respect to the functional role of E beta in driving alpha beta T cell differentiation and the mechanism of alpha beta T lineage commitment. ..
  45. Jacobs N, Chen R, Gubser C, Najarro P, Smith G. Intradermal immune response after infection with Vaccinia virus. J Gen Virol. 2006;87:1157-61 pubmed
    ..This report is the first to characterize the local immune response sequence to VACV infection and represents a benchmark against which the responses induced by genetically modified VACVs may be compared. ..
  46. Holman P, Lacy M, Roth M, Kranz D. Mechanisms that generate junctional diversity in alpha and delta chains that use the Tcrd-V3 gene product. Immunogenetics. 1992;35:33-40 pubmed
    ..Finally, a comparison of the variable domains of these alpha and delta chains shows that a notable difference is the variability in length of the CDR 3 region which can be significantly longer in delta-chains than in alpha-chains. ..
  47. Malissen M, Pereira P, Gerber D, Malissen B, DiSanto J. The common cytokine receptor gamma chain controls survival of gamma/delta T cells. J Exp Med. 1997;186:1277-85 pubmed
  48. Kang J, Coles M, Cado D, Raulet D. The developmental fate of T cells is critically influenced by TCRgammadelta expression. Immunity. 1998;8:427-38 pubmed
    ..To resolve this paradox, we provide evidence for a minor population of gammadelta-dependent alphabeta-lineage cells in normal mice. The results indicate that the T cell lineage commitment process is either error-prone or stochastic. ..
  49. Jimenez M, Martinez C, Ercilla G, Carreras E, Urbano Ispizua A, Aymerich M, et al. Clinical factors influencing T-cell receptor excision circle (TRECs) counts following allogeneic stem cell transplantation in adults. Transpl Immunol. 2006;16:52-9 pubmed
    ..032). Our data support the concept that adult thymus contributes with a slow but continuous production of thymic T cells to immune reconstitution after SCT. Chronic GVHD is the main factor associated to a delay in TRECs counts recovery. ..
  50. Masternak M, Przybylski G, Smoczkiewicz P, Płotek W, Kowalczyk D, Nowak J. Novel competitive PCR methods for quantitation of T-cell receptor delta (TCRD) gene rearrangements. J Appl Genet. 2002;43:235-44 pubmed
    ..We showed that the rgc-PCR and cpc-PCR are reliable and give reproducible results. The methods do not require any expensive equipment or reagents, and can be used to determine the frequency of gene rearrangements. ..
  51. Chauhan S, Tripathy N, Sinha N, Nityanand S. T-cell receptor repertoire of circulating gamma delta T-cells in Takayasu's arteritis. Clin Immunol. 2006;118:243-9 pubmed
    ..Our data show that gammadelta T-cells particularly those bearing Vdelta1 TCR may have an important role in the immunopathogenesis of TA. ..
  52. Hashimoto M, Yamashita Y, Mori N. Immunohistochemical detection of CD79a expression in precursor T cell lymphoblastic lymphoma/leukaemias. J Pathol. 2002;197:341-7 pubmed
    ..These results suggest that CD79a is expressed weakly and transiently in immature T-lineage cells. ..
  53. Maia A, van der Velden V, Harrison C, Szczepanski T, Williams M, Griffiths M, et al. Prenatal origin of hyperdiploid acute lymphoblastic leukemia in identical twins. Leukemia. 2003;17:2202-6 pubmed
    ..It is likely that one or more additional postnatal genetic events was required for overt leukemogenesis. ..