t lymphocyte gene rearrangement


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

Top Publications

  1. Brochet X, Lefranc M, Giudicelli V. IMGT/V-QUEST: the highly customized and integrated system for IG and TR standardized V-J and V-D-J sequence analysis. Nucleic Acids Res. 2008;36:W503-8 pubmed publisher
    ..The 'Advanced parameters' allow to modify default parameters used by IMGT/V-QUEST and IMGT/JunctionAnalysis according to the users' interest. IMGT/V-QUEST is freely available for academic research at http://imgt.cines.fr. ..
  2. Giudicelli V, Duroux P, Ginestoux C, Folch G, Jabado Michaloud J, Chaume D, et al. IMGT/LIGM-DB, the IMGT comprehensive database of immunoglobulin and T cell receptor nucleotide sequences. Nucleic Acids Res. 2006;34:D781-4 pubmed
    ..They represent the main source of IG and TR gene and allele knowledge stored in IMGT/GENE-DB and in the IMGT reference directory. IMGT/LIGM-DB is freely available at http://imgt.cines.fr. ..
  3. Hodges E, Krishna M, Pickard C, Smith J. Diagnostic role of tests for T cell receptor (TCR) genes. J Clin Pathol. 2003;56:1-11 pubmed
    ..It will also describe various methods that are currently used to study T cell populations in body fluids and tissue, their diagnostic role, and current limitations of the methodology. ..
  4. Cowell L, Davila M, Ramsden D, Kelsoe G. Computational tools for understanding sequence variability in recombination signals. Immunol Rev. 2004;200:57-69 pubmed
    ..These models successfully predict RS activity and identify functional, cryptic RSs (cRSs). These models permit studies to identify RSs and cRSs for empiric study and constitute a tool useful for understanding RS structure and function. ..
  5. Bezbradica J, Hill T, Stanic A, Van Kaer L, Joyce S. Commitment toward the natural T (iNKT) cell lineage occurs at the CD4+8+ stage of thymic ontogeny. Proc Natl Acad Sci U S A. 2005;102:5114-9 pubmed
  6. Zuna J, Muzikova K, Ford A, Maia A, Krejci O, Tousovska K, et al. Pre-natal, clonal origin of acute lymphoblastic leukaemia in triplets. Leuk Lymphoma. 2003;44:2099-102 pubmed
    ..Differences in IGH rearrangements in diagnostic samples also indicates divergent subclonal evolution of the original "pre-leukaemic" clone. ..
  7. van Dongen J, Langerak A, Bruggemann M, Evans P, Hummel M, Lavender F, et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia. 2003;17:2257-317 pubmed
    ..The BIOMED-2 multiplex tubes can now be used for diagnostic clonality studies as well as for the identification of PCR targets suitable for the detection of minimal residual disease. ..
  8. Venturi V, Price D, Douek D, Davenport M. The molecular basis for public T-cell responses?. Nat Rev Immunol. 2008;8:231-8 pubmed publisher
  9. Bender T, Kremer C, Kraus M, Buch T, Rajewsky K. Critical functions for c-Myb at three checkpoints during thymocyte development. Nat Immunol. 2004;5:721-9 pubmed
    ..Thus, c-Myb is essential at several stages during T cell development in the thymus. ..

More Information


  1. Cowell L, Davila M, Kepler T, Kelsoe G. Identification and utilization of arbitrary correlations in models of recombination signal sequences. Genome Biol. 2002;3:RESEARCH0072 pubmed
    ..The approach could be equally powerful for the study of promoter and enhancer elements, splice sites, and other DNA regulatory sites that are highly variable at the level of individual nucleotide positions. ..
  2. Giudicelli V, Chaume D, Lefranc M. IMGT/V-QUEST, an integrated software program for immunoglobulin and T cell receptor V-J and V-D-J rearrangement analysis. Nucleic Acids Res. 2004;32:W435-40 pubmed
    ..IMGT/V-QUEST is currently available for human and mouse, and partly for non-human primates, sheep, chondrichthyes and teleostei. IMGT/V-QUEST is freely available at http://imgt.cines.fr. ..
  3. Bleakley K, Giudicelli V, Wu Y, Lefranc M, Biau G. IMGT standardization for statistical analyses of T cell receptor junctions: the TRAV-TRAJ example. In Silico Biol. 2006;6:573-88 pubmed
    ..Using statistical learning, we constructed an automatic warning system to predict if new, automatically analysed TRAV-TRAJ sequences should be manually re-checked. We estimated the robustness of this automatic warning system. ..
  4. Yousfi Monod M, Giudicelli V, Chaume D, Lefranc M. IMGT/JunctionAnalysis: the first tool for the analysis of the immunoglobulin and T cell receptor complex V-J and V-D-J JUNCTIONs. Bioinformatics. 2004;20 Suppl 1:i379-85 pubmed
    ..IMGT/JunctionAnalysis is available from the IMGT Home page at http://imgt.cines.fr ..
  5. Ponchel F, Verburg R, Bingham S, Brown A, Moore J, Protheroe A, et al. Interleukin-7 deficiency in rheumatoid arthritis: consequences for therapy-induced lymphopenia. Arthritis Res Ther. 2005;7:R80-92 pubmed
  6. Arstila T, Casrouge A, Baron V, Even J, Kanellopoulos J, Kourilsky P. A direct estimate of the human alphabeta T cell receptor diversity. Science. 1999;286:958-61 pubmed
    ..Thus, the naïve repertoire is highly diverse, whereas the memory compartment, here one-third of the T cell population, contributes less than 1 percent of the total diversity. ..
  7. Asarnow D, Goodman T, Lefrancois L, Allison J. Distinct antigen receptor repertoires of two classes of murine epithelium-associated T cells. Nature. 1989;341:60-2 pubmed
    ..The distinctive features of these two populations suggest that they develop or are selected differently for particular tissue-specific functions. ..
  8. Mertsching E, Burdet C, Ceredig R. IL-7 transgenic mice: analysis of the role of IL-7 in the differentiation of thymocytes in vivo and in vitro. Int Immunol. 1995;7:401-14 pubmed
    ..We conclude that IL-7 is probably not an important differentiation factor for immature mouse thymocytes. ..
  9. Okamoto Y, Douek D, McFarland R, Koup R. Effects of exogenous interleukin-7 on human thymus function. Blood. 2002;99:2851-8 pubmed
    ..Our results provide compelling evidence that IL-7 has a direct effect on increasing TCR-alphabeta rearrangement and indicate the potential use of IL-7 for enhancing de novo naïve T-cell generation in immunocompromised patients. ..
  10. Nussenzweig A, Chen C, da Costa Soares V, Sanchez M, Sokol K, Nussenzweig M, et al. Requirement for Ku80 in growth and immunoglobulin V(D)J recombination. Nature. 1996;382:551-5 pubmed
    ..The unexpected growth phenotype suggests a new and important link between Ku80 and growth control. ..
  11. Oettinger M, Schatz D, Gorka C, Baltimore D. RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination. Science. 1990;248:1517-23 pubmed
    ..RAG-1 and RAG-2 might activate the expression of the V(D)J recombinase but, more likely, they directly participate in the recombination reaction. ..
  12. Dudley E, Girardi M, Owen M, Hayday A. Alpha beta and gamma delta T cells can share a late common precursor. Curr Biol. 1995;5:659-69 pubmed
    ..In contrast, successful rearrangement of the TCR beta locus remains compatible with cells becoming either gamma delta or alpha beta T cells. ..
  13. Bogue M, Zhu C, Aguilar Cordova E, Donehower L, Roth D. p53 is required for both radiation-induced differentiation and rescue of V(D)J rearrangement in scid mouse thymocytes. Genes Dev. 1996;10:553-65 pubmed
    ..These results suggest that exposure to ionizing radiation facilitates a partial bypass of the scid defect, perhaps by inducing p53-dependent DNA damage response pathways. ..
  14. Livak F, Tourigny M, Schatz D, Petrie H. Characterization of TCR gene rearrangements during adult murine T cell development. J Immunol. 1999;162:2575-80 pubmed
    ..Further, because TCR gene rearrangements are generally limited to T lineage cells, these analyses provide molecular evidence that irreversible commitment to the T lineage can occur as early as the CD44highCD25+ stage of development. ..
  15. Lambolez F, Azogui O, Joret A, Garcia C, von Boehmer H, Di Santo J, et al. Characterization of T cell differentiation in the murine gut. J Exp Med. 2002;195:437-49 pubmed
    ..Finally, only 3% of CP cells were clearly involved in T cell differentiation, suggesting that these structures may have additional physiological roles in the gut. ..
  16. Ye S, Agata Y, Lee H, Kurooka H, Kitamura T, Shimizu A, et al. The IL-7 receptor controls the accessibility of the TCRgamma locus by Stat5 and histone acetylation. Immunity. 2001;15:813-23 pubmed
    ..Therefore, these results suggest that Stat5 may recruit the transcriptional coactivators to the Jgamma germline promoter and control the accessibility of the TCRgamma locus by histone acetylation. ..
  17. Zhu C, Bogue M, Lim D, Hasty P, Roth D. Ku86-deficient mice exhibit severe combined immunodeficiency and defective processing of V(D)J recombination intermediates. Cell. 1996;86:379-89 pubmed
    ..We suggest that Ku86 may be required to remodel or disassemble DNA-protein complexes containing broken ends, making them available for further processing and joining. ..
  18. Yagi T, Hibi S, Tabata Y, Kuriyama K, Teramura T, Hashida T, et al. Detection of clonotypic IGH and TCR rearrangements in the neonatal blood spots of infants and children with B-cell precursor acute lymphoblastic leukemia. Blood. 2000;96:264-8 pubmed
    ..Our findings strongly suggest a prenatal origin for some cases of B-cell precursor ALL lacking specific clonotypic abnormalities...
  19. Veiga Fernandes H, Walter U, Bourgeois C, McLean A, Rocha B. Response of naïve and memory CD8+ T cells to antigen stimulation in vivo. Nat Immunol. 2000;1:47-53 pubmed
    ..These special properties of memory T cells ensure the immediate control of reinfection. ..
  20. Mombaerts P, Iacomini J, Johnson R, Herrup K, Tonegawa S, Papaioannou V. RAG-1-deficient mice have no mature B and T lymphocytes. Cell. 1992;68:869-77 pubmed
    ..Although RAG-1 expression has been reported in the central nervous system of the mouse, no obvious neuroanatomical or behavioral abnormalities have been found in the RAG-1-deficient mice. ..
  21. Shinkai Y, Rathbun G, Lam K, Oltz E, Stewart V, Mendelsohn M, et al. RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell. 1992;68:855-67 pubmed
    ..Because the SCID phenotype was the only obvious abnormality detected in RAG-2 mutant mice, RAG-2 function and V(D)J recombinase activity, per se, are not required for development of cells other than lymphocytes. ..
  22. King A, Kondo M, Scherer D, Weissman I. Lineage infidelity in myeloid cells with TCR gene rearrangement: a latent developmental potential of proT cells revealed by ectopic cytokine receptor signaling. Proc Natl Acad Sci U S A. 2002;99:4508-13 pubmed
    ..In addition, Dbeta1 and Dbeta2 DJ rearrangement of the TCRbeta gene may be differentially regulated and thus serve as markers for distinct proT cell maturational stages. ..
  23. Kouskoff V, Nemazee D. Role of receptor editing and revision in shaping the B and T lymphocyte repertoire. Life Sci. 2001;69:1105-13 pubmed
    ..Recent studies have likewise suggested a role for receptor editing and revision in shaping the T cell repertoire during development and tolerance. ..
  24. Mak T, Hakem A, McPherson J, Shehabeldin A, Zablocki E, Migon E, et al. Brca1 required for T cell lineage development but not TCR loci rearrangement. Nat Immunol. 2000;1:77-82 pubmed
    ..Thus, the outcome of Brca1 deficiency was dependent on cellular context, with the major defects being increased apoptosis in thymocytes, and defective proliferation in peripheral T cells. ..
  25. Gu Y, Seidl K, Rathbun G, Zhu C, Manis J, van der Stoep N, et al. Growth retardation and leaky SCID phenotype of Ku70-deficient mice. Immunity. 1997;7:653-65 pubmed
    ..These unanticipated features of the Ku70-deficient phenotype with respect to lymphocyte development and V(D)J recombination may reflect differential functions of the three DNA-PK components. ..
  26. Raulet D. The structure, function, and molecular genetics of the gamma/delta T cell receptor. Annu Rev Immunol. 1989;7:175-207 pubmed
  27. Schatz D, Oettinger M, Baltimore D. The V(D)J recombination activating gene, RAG-1. Cell. 1989;59:1035-48 pubmed
    ..RAG-1 may activate V(D)J recombination indirectly, or it may encode the V(D)J recombinase itself. ..
  28. Cianci R, Spada C, Perri V, Cammarota G, Urgesi R, Lolli S, et al. Active thymopoiesis in idiopathic chronic pancreatitis. Eur Rev Med Pharmacol Sci. 2008;12:41-6 pubmed
    ..Our data show that naive TREC+ cells are normally represented in CP. The presence of active thymopoiesis may be the underlying mechanism resulting in continuous production of T-cells, responsible of maintaining the inflammatory process. ..
  29. Hu T, Simmons A, Yuan J, Bender T, Alberola Ila J. The transcription factor c-Myb primes CD4+CD8+ immature thymocytes for selection into the iNKT lineage. Nat Immunol. 2010;11:435-41 pubmed publisher
    ..Here we show that the transcription factor c-Myb has a central role in priming DP thymocytes to enter the iNKT lineage by simultaneously regulating CD1d expression, the half-life of DP cells and expression of SLAMF1, SLAMF6 and SAP. ..
  30. Oshtory S, Apisarnthanarax N, Gilliam A, Cooper K, Meyerson H. Usefulness of flow cytometry in the diagnosis of mycosis fungoides. J Am Acad Dermatol. 2007;57:454-62 pubmed
    ..Small study size was a limitation. Flow cytometry of skin biopsy specimens is a sensitive method for detecting abnormalities in MF and should be considered part of the routine workup of patients with a clinical suggestion of MF. ..
  31. Yelamos J, Monreal Y, Saenz L, Aguado E, Schreiber V, Mota R, et al. PARP-2 deficiency affects the survival of CD4+CD8+ double-positive thymocytes. EMBO J. 2006;25:4350-60 pubmed
  32. Matei I, Guidos C, Danska J. ATM-dependent DNA damage surveillance in T-cell development and leukemogenesis: the DSB connection. Immunol Rev. 2006;209:142-58 pubmed
    ..Here, we review recent evidence providing insight into the mechanisms by which ATM promotes normal lymphocyte development and protects from neoplastic transformation. ..
  33. Lima K, Abrahamsen T, Foelling I, Natvig S, Ryder L, Olaussen R. Low thymic output in the 22q11.2 deletion syndrome measured by CCR9+CD45RA+ T cell counts and T cell receptor rearrangement excision circles. Clin Exp Immunol. 2010;161:98-107 pubmed publisher
    ..88) in patients without an identifiable thymus. Production of RTEs is impaired in patients with a 22q11.2 deletion, and CCR9 appears to be a good marker for RTE-related T cells. ..
  34. Parra Z, Arnold T, Nowak M, Hellman L, Miller R. TCR gamma chain diversity in the spleen of the duckbill platypus (Ornithorhynchus anatinus). Dev Comp Immunol. 2006;30:699-710 pubmed
    ..Monotreme TRGC regions also had among the most variation in the length of the connecting peptide region described for any species due to repeated motifs...
  35. Litman G, Cannon J, Rast J. New insights into alternative mechanisms of immune receptor diversification. Adv Immunol. 2005;87:209-36 pubmed
    ..Unusual genetic mechanisms for diversifying recognition proteins may be a widespread characteristic of animal immunity. ..
  36. Li Y, Chen S, Yang L, Zhou Y, Wu X, Huang M, et al. Clonal expanded TCR Vbeta T cells in patients with APL. Hematology. 2005;10:135-9 pubmed
    ..The clonal expansion of T-cells were considered to be a specific anti-leukemic immune response by host T-cells activated by the leukemia-associated-antigen. ..
  37. Kerst G, Kreyenberg H, Roth C, Well C, Dietz K, Coustan Smith E, et al. Concurrent detection of minimal residual disease (MRD) in childhood acute lymphoblastic leukaemia by flow cytometry and real-time PCR. Br J Haematol. 2005;128:774-82 pubmed
    ..We conclude that both MRD assays yield generally concordant results. Their combined use should enable MRD monitoring in virtually all patients and prevent false-negative results due to clonal evolution or phenotypic shifts. ..
  38. Ege M, Ma Y, Manfras B, Kalwak K, Lu H, Lieber M, et al. Omenn syndrome due to ARTEMIS mutations. Blood. 2005;105:4179-86 pubmed
  39. Nihal M, Mikkola D, Horvath N, Gilliam A, Stevens S, Spiro T, et al. Cutaneous lymphoid hyperplasia: a lymphoproliferative continuum with lymphomatous potential. Hum Pathol. 2003;34:617-22 pubmed
    ..The high prevalence of dominant clonality in our series may have resulted from the sensitivity of our PCR assays as well as patient selection. ..
  40. Oettinger M. How to keep V(D)J recombination under control. Immunol Rev. 2004;200:165-81 pubmed
    ..The major focus of this review is on accessibility control and the role of chromatin and nuclear architecture in achieving this regulation, although other issues are touched upon. ..
  41. Madhok A, Chandrasekran A, Parnell V, Gandhi M, Chowdhury D, Pahwa S. Levels of recent thymic emigrant cells decrease in children undergoing partial thymectomy during cardiac surgery. Clin Diagn Lab Immunol. 2005;12:563-5 pubmed
    ..While decreased thymic output may persist, the long-term implications were not evaluated in this patient population. ..
  42. Ferrante P, Delbue S, Pagani E, Mancuso R, Marzocchetti A, Borghi E, et al. Analysis of JC virus genotype distribution and transcriptional control region rearrangements in human immunodeficiency virus-positive progressive multifocal leukoencephalopathy patients with and without highly active antiretroviral treatment. J Neurovirol. 2003;9 Suppl 1:42-6 pubmed
    ..The data obtained indicate that the introduction of HAART has induced changes in JCV genotype distribution and probably reduced the rate of rearrangements of TCR region among PML patients. ..
  43. Dujka M, Puebla Osorio N, Tavana O, Sang M, Zhu C. ATM and p53 are essential in the cell-cycle containment of DNA breaks during V(D)J recombination in vivo. Oncogene. 2010;29:957-65 pubmed publisher
    ..This study shows the dynamic multiple functions of ATM in maintaining genomic stability and preventing tumorigenesis in developing lymphocytes. ..
  44. Mancebo E, Clemente J, Sanchez J, Ruiz Contreras J, de Pablos P, Cortezon S, et al. Longitudinal analysis of immune function in the first 3 years of life in thymectomized neonates during cardiac surgery. Clin Exp Immunol. 2008;154:375-83 pubmed publisher
    ..This could produce a compromise in immune function later in life, especially if the patients suffer T cell depletion and need a reconstitution of immune function. ..
  45. Belousova I, Kazakov D, Sosna B, Sulc M, Michal M. [Small-cell variant of CD30+ -anaplastic large-cell lymphoma of the skin]. Arkh Patol. 2008;70:40-3 pubmed
    ..Chemotherapy was performed and finally the patient underwent allogenic bone marrow transplantation; he died 3 years after the original diagnosis due to acute graft-versus-host disease and sepsis. ..
  46. Dereure O, Balavoine M, Salles M, Candon Kerlau S, Clot J, Guilhou J, et al. Correlations between clinical, histologic, blood, and skin polymerase chain reaction outcome in patients treated for mycosis fungoides. J Invest Dermatol. 2003;121:614-7 pubmed
    ..This study confirms frequent detection of a dominant gene rearrangement in peripheral blood in MF patients and shows that PCR may remain positive in lesional sites even when skin lesions are successfully treated. ..
  47. Traggiai E, Chicha L, Mazzucchelli L, Bronz L, Piffaretti J, Lanzavecchia A, et al. Development of a human adaptive immune system in cord blood cell-transplanted mice. Science. 2004;304:104-7 pubmed
    ..This provides a valuable model to study development and function of the human adaptive immune system in vivo. ..
  48. Tan S, Sim C, Ong B, Sander C. Follicular mycosis fungoides mimicking a cutaneous B-cell lymphoproliferative disorder. Australas J Dermatol. 2004;45:188-91 pubmed
    ..This case illustrates a variant of MF that has a more rapid progression than the otherwise indolent course of classical MF over many years, and the diagnostic pitfalls, whereby the histology can mimic a B-cell proliferative disorder. ..
  49. Krause J, Shahidi Asl M. Molecular pathology in the diagnosis and treatment of non-Hodgkin's lymphomas. J Cell Mol Med. 2003;7:494-512 pubmed
    ..The molecular pathology of the non-Hodgkin's lymphomas is discussed. ..
  50. Criscitiello M, Kamper S, McKinney E. Allelic polymorphism of TCRalpha chain constant domain genes in the bicolor damselfish. Dev Comp Immunol. 2004;28:781-92 pubmed
    ..These data suggest that our understanding of the function of the TCR constant domains of these vertebrates is incomplete. ..
  51. Cox C, Diamanti P, Evely R, Kearns P, Blair A. Expression of CD133 on leukemia-initiating cells in childhood ALL. Blood. 2009;113:3287-96 pubmed publisher
    ..These data suggest that leukemia-initiating cells in childhood B-ALL have a primitive CD133(+)/CD19(-) and CD38(-) phenotype. ..
  52. Karrman K, Forestier E, Heyman M, Andersen M, Autio K, Blennow E, et al. Clinical and cytogenetic features of a population-based consecutive series of 285 pediatric T-cell acute lymphoblastic leukemias: rare T-cell receptor gene rearrangements are associated with poor outcome. Genes Chromosomes Cancer. 2009;48:795-805 pubmed publisher
    ..However, further prospective and collaborative investigations of this genetically heterogeneous entity are needed to confirm these results. ..
  53. Hunzeker C, Fangman W, Latkowski J. Folliculotropic mycosis fungoides. Dermatol Online J. 2007;13:5 pubmed
    ..Folliculotropic MF may be more resistant to superficial therapies because of the depth of the neoplastic T-cells in the follicle. ..