alpha chain t cell antigen receptor gene rearrangement

Summary

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

Top Publications

  1. Huang C, Kanagawa O. Ordered and coordinated rearrangement of the TCR alpha locus: role of secondary rearrangement in thymic selection. J Immunol. 2001;166:2597-601 pubmed
    ..Thus, the lack of allelic exclusion and TCR alpha secondary rearrangement play a key role in the formation of a functional T cell repertoire. ..
  2. Petrie H, Livak F, Burtrum D, Mazel S. T cell receptor gene recombination patterns and mechanisms: cell death, rescue, and T cell production. J Exp Med. 1995;182:121-7 pubmed
  3. Hawwari A, Krangel M. Role for rearranged variable gene segments in directing secondary T cell receptor alpha recombination. Proc Natl Acad Sci U S A. 2007;104:903-7 pubmed
    ..The data provide the mechanistic basis for a model of primary and secondary T cell receptor alpha recombination in which recombination events progress in multiple small steps down the Jalpha array. ..
  4. Guo J, Hawwari A, Li H, Sun Z, Mahanta S, Littman D, et al. Regulation of the TCRalpha repertoire by the survival window of CD4(+)CD8(+) thymocytes. Nat Immunol. 2002;3:469-76 pubmed
    ..Rather, it limits the progression of rearrangement along the J(alpha) locus and the opportunities for positive selection, thereby regulating the TCRalpha repertoire. ..
  5. Starr T, Jameson S, Hogquist K. Positive and negative selection of T cells. Annu Rev Immunol. 2003;21:139-76 pubmed
    ..We also discuss emerging data on the selection of regulatory T cells. Such cells require a high-affinity interaction with self-antigens, yet differentiate into regulatory cells instead of being eliminated. ..
  6. 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. ..
  7. 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. ..
  8. Lacorazza H, Tucek Szabo C, Vasovic L, Remus K, Nikolich Zugich J. Premature TCR alpha beta expression and signaling in early thymocytes impair thymocyte expansion and partially block their development. J Immunol. 2001;166:3184-93 pubmed
  9. 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. ..

More Information

Publications62

  1. Mancini S, Candéias S, Di Santo J, Ferrier P, Marche P, Jouvin Marche E. TCRA gene rearrangement in immature thymocytes in absence of CD3, pre-TCR, and TCR signaling. J Immunol. 2001;167:4485-93 pubmed
    ..Taken together, these results provide new insights into the molecular control of early T cell differentiation. ..
  2. Fuschiotti P, Pasqual N, Hierle V, Borel E, London J, Marche P, et al. Analysis of the TCR alpha-chain rearrangement profile in human T lymphocytes. Mol Immunol. 2007;44:3380-8 pubmed
  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. 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. ..
  5. Pasqual N, Gallagher M, Aude Garcia C, Loiodice M, Thuderoz F, Demongeot J, et al. Quantitative and qualitative changes in V-J alpha rearrangements during mouse thymocytes differentiation: implication for a limited T cell receptor alpha chain repertoire. J Exp Med. 2002;196:1163-73 pubmed
    ..These results provide a new insight into TCR alpha repertoire size and suggest a scenario for V usage during differentiation. ..
  6. Mauvieux L, Villey I, de Villartay J. TEA regulates local TCR-Jalpha accessibility through histone acetylation. Eur J Immunol. 2003;33:2216-22 pubmed
    ..TEA-dependent histone acetylation of the most upstream Jalpha segments leads to enhanced DNA accessibility thus optimizing TCRJalpha usage and increasing Ag receptor diversity potential. ..
  7. Pircher H, Rebai N, Groettrup M, Gregoire C, Speiser D, Happ M, et al. Preferential positive selection of V alpha 2+ CD8+ T cells in mouse strains expressing both H-2k and T cell receptor V alpha a haplotypes: determination with a V alpha 2-specific monoclonal antibody. Eur J Immunol. 1992;22:399-404 pubmed
  8. 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. ..
  9. Mauvieux L, Villey I, de Villartay J. T early alpha (TEA) regulates initial TCRVAJA rearrangements and leads to TCRJA coincidence. Eur J Immunol. 2001;31:2080-6 pubmed
    ..In a model of multiple waves of TCRVAJA recombination, this cis-regulatory effect of TEA allows for the scanning of the entire TCRJA cluster, thereby increasing the TCR alpha/beta diversity potential. ..
  10. Fukui Y, Hashimoto O, Inayoshi A, Gyotoku T, Sano T, Koga T, et al. Highly restricted T cell repertoire shaped by a single major histocompatibility complex-peptide ligand in the presence of a single rearranged T cell receptor beta chain. J Exp Med. 1998;188:897-907 pubmed
    ..Our findings provide definitive evidence that specific recognition of self-peptides by TCR could be involved in positive selection of thymocytes. ..
  11. Wang F, Huang C, Kanagawa O. Rapid deletion of rearranged T cell antigen receptor (TCR) Valpha-Jalpha segment by secondary rearrangement in the thymus: role of continuous rearrangement of TCR alpha chain gene and positive selection in the T cell repertoire formation. Proc Natl Acad Sci U S A. 1998;95:11834-9 pubmed
    ..These results suggest that secondary rearrangements of the TCR alpha chain gene play an important role in the formation of the T cell repertoire. ..
  12. Williams A, Bland P, Phillips A, Turner S, Brooklyn T, Shaya G, et al. Intestinal alpha beta T cells differentiate and rearrange antigen receptor genes in situ in the human infant. J Immunol. 2004;173:7190-9 pubmed
    ..Thus, mucosal T cell responsiveness to environmental Ag is shaped in situ during early life. ..
  13. Davodeau F, Difilippantonio M, Roldan E, Malissen M, Casanova J, Couedel C, et al. The tight interallelic positional coincidence that distinguishes T-cell receptor Jalpha usage does not result from homologous chromosomal pairing during ValphaJalpha rearrangement. EMBO J. 2001;20:4717-29 pubmed
  14. Buch T, Rieux Laucat F, Forster I, Rajewsky K. Failure of HY-specific thymocytes to escape negative selection by receptor editing. Immunity. 2002;16:707-18 pubmed
    ..In the absence of the restricting MHC element, however, developing thymocytes replaced the inserted TCR alpha exon efficiently. ..
  15. Burns R, Natarajan K, LoCascio N, O Brien D, Kobori J, Shastri N, et al. Molecular analysis of skewed Tcra-V gene use in T-cell receptor beta-chain transgenic mice. Immunogenetics. 1998;47:107-14 pubmed
  16. 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. ..
  17. Villey I, Caillol D, Selz F, Ferrier P, de Villartay J. 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;5:331-42 pubmed
    ..These results are consistent with TEA acting as a "rearrangement-focusing" element, targeting the primary waves of V alpha-J alpha recombination to the most 5' J alpha S in an ongoing TCR-J alpha rearrangement model. ..
  18. Hawwari A, Bock C, Krangel M. Regulation of T cell receptor alpha gene assembly by a complex hierarchy of germline Jalpha promoters. Nat Immunol. 2005;6:481-9 pubmed
    ..Central promoter derepression also occurred after primary rearrangement, thereby providing a mechanism to target secondary recombination events. ..
  19. Wang C, Bogue M, Nguyen A, Roth D. Irradiation-induced rescue of thymocyte differentiation and V(D)J recombination in mice lacking the catalytic subunit of DNA-dependent protein kinase. J Immunol. 1999;163:6065-71 pubmed
    ..To test this hypothesis, we examined the effects of irradiation on DNA-PKcs-deficient (slip) mice. Our data provide the first evidence that DNA-PKcs is not required for limited rescue of thymocyte differentiation or TCR rearrangements. ..
  20. Holman P, Walsh E, Hogquist K. The central tolerance response to male antigen in normal mice is deletion and not receptor editing. J Immunol. 2003;171:4048-53 pubmed
    ..Thus, it would appear that receptor editing is not a predominant tolerance mechanism for this self-Ag. ..
  21. Hamrouni A, Olsson A, Wiegers G, Villunger A. Impact of cellular lifespan on the T cell receptor repertoire. Eur J Immunol. 2007;37:1978-85 pubmed
    ..However, the changes that we observed were less pronounced than those found in lck-bcl-x(L) transgenic mice, pointing towards qualitative differences between Bcl-2- and Bcl-x(L)-mediated cell death inhibition during T cell development. ..
  22. De Silva Udawatta M, Kumar S, Greidinger E, Hoffman R. Cloned human TCR from patients with autoimmune disease can respond to two structurally distinct autoantigens. J Immunol. 2004;172:3940-7 pubmed
    ..These studies support an important role of plasticity of the TCR in the development of human autoimmunity. ..
  23. Chen Z, Shen L, Regan J, Kou Z, Ghim S, Letvin N. The T cell receptor gene usage by simian immunodeficiency virus gag-specific cytotoxic T lymphocytes in rhesus monkeys. J Immunol. 1996;156:1469-75 pubmed
    ..Such a broad CTL-TCR repertoire may be advantageous for the host in containing an AIDS virus infection. ..
  24. Wang K, Klotz J, Kiser G, Bristol G, Hays E, Lai E, et al. Organization of the V gene segments in mouse T-cell antigen receptor alpha/delta locus. Genomics. 1994;20:419-28 pubmed
    ..These data provide information on the evolution of the alpha/delta locus and on organization features that might influence the expression of specific V gene segments in gamma delta cells. ..
  25. Yague J, Blackman M, Born W, Marrack P, Kappler J, Palmer E. The structure of V alpha and J alpha segments in the mouse. Nucleic Acids Res. 1988;16:11355-64 pubmed
    ..Among these cDNA clones, we have found 4 J alpha and 4 V alpha sequences that have not yet been described. The relationship of these "new" gene segments to those already characterized is discussed. ..
  26. Yoshida M, Iwahori T, Nakabayashi I, Akashi M, Watanabe T, Yoshikawa N. In vitro production of myeloperoxidase anti-neutrophil cytoplasmic antibody and establishment of Th1-type T cell lines from peripheral blood lymphocytes of patients. Clin Exp Rheumatol. 2005;23:227-30 pubmed
    ..Our results suggest that Th1-type T cells may mediate MPO-ANCA production, and may play a role in the onset of MPO-ANCA vasculitis. ..
  27. Thomas H, Irawaty W, Darwiche R, Brodnicki T, Santamaria P, Allison J, et al. IL-1 receptor deficiency slows progression to diabetes in the NOD mouse. Diabetes. 2004;53:113-21 pubmed
    ..3 TCR transgenic NOD mice but prolonged the time to diabetes in BDC2.5 TCR transgenic NOD mice. We conclude that IL-1R deficiency slows progression to diabetes in NOD mice but on its own does not prevent diabetes. ..
  28. Standifer N, Kraig E, Infante A. A hierarchy of T cell receptor motifs determines responsiveness to the immunodominant epitope in experimental autoimmune myasthenia gravis. J Neuroimmunol. 2003;145:68-76 pubmed
    ..Analysis of T cell clones demonstrated a fourfold higher avidity of Vbeta6+ than non-Vbeta6 cells for Talpha146-162 indicating that a hierarchy of TCR motifs determines T cell responsiveness in EAMG. ..
  29. Pauza M, Dobbs C, He J, Patterson T, Wagner S, Anobile B, et al. T-cell receptor transgenic response to an endogenous polymorphic autoantigen determines susceptibility to diabetes. Diabetes. 2004;53:978-88 pubmed
    ..Thus, the generation of 6.9TCR transgenic mice provides a model of autoimmune diabetes whereby controlled expression of an endogenous polymorphic autoantigen effectively determines disease development. ..
  30. Matsuda J, Gapin L, Baron J, Sidobre S, Stetson D, Mohrs M, et al. Mouse V alpha 14i natural killer T cells are resistant to cytokine polarization in vivo. Proc Natl Acad Sci U S A. 2003;100:8395-400 pubmed
  31. Kang H, Liesenfeld O, Remington J, Claflin J, Wang X, Suzuki Y. TCR V beta 8+ T cells prevent development of toxoplasmic encephalitis in BALB/c mice genetically resistant to the disease. J Immunol. 2003;170:4254-9 pubmed
    ..Thus, Vbeta8(+) T cells appear to play a crucial role in the genetic resistance of BALB/c mice against development of TE. ..
  32. Mars L, Laloux V, Goude K, Desbois S, Saoudi A, Van Kaer L, et al. Cutting edge: V alpha 14-J alpha 281 NKT cells naturally regulate experimental autoimmune encephalomyelitis in nonobese diabetic mice. J Immunol. 2002;168:6007-11 pubmed
    ..Our findings indicate that enrichment and/or stimulation of CD1d-dependent NKT cells may be used as a novel strategy to treat CNS autoimmunity. ..
  33. Warmflash A, Weigert M, Dinner A. Control of genotypic allelic inclusion through TCR surface expression. J Immunol. 2005;175:6412-9 pubmed
    ..This feature of the model makes clear that allelic inclusion does not in itself compromise central tolerance. A specific experiment based on modulation of TCR surface expression levels is proposed to test the model. ..
  34. Kitaura K, Kanayama K, Fujii Y, Shiobara N, Tanaka K, Kurane I, et al. T cell receptor repertoire in BALB/c mice varies according to tissue type, sex, age, and hydrocortisone treatment. Exp Anim. 2009;58:159-68 pubmed
    ..The present findings suggest that the HC susceptibility of immature thymic T cells is different between TCR families. ..
  35. Levin S, Anderson S, Forbush K, Perlmutter R. A dominant-negative transgene defines a role for p56lck in thymopoiesis. EMBO J. 1993;12:1671-80 pubmed
    ..These results suggest that p56lck normally regulates T cell production by metering the replicative potential of immature thymoblasts. ..
  36. Kaye J, Vasquez N, Hedrick S. Involvement of the same region of the T cell antigen receptor in thymic selection and foreign peptide recognition. J Immunol. 1992;148:3342-53 pubmed
    ..The findings presented here are discussed in relation to the possible role of self-peptides in positive selection. ..
  37. Bosco N, Hung H, Pasqual N, Jouvin Marche E, Marche P, Gascoigne N, et al. Role of the T cell receptor alpha chain in the development and phenotype of naturally arising CD4+CD25+ T cells. Mol Immunol. 2006;43:246-54 pubmed
  38. DiRienzo C, Murphy G, Jones S, Korngold R, Friedman T. T-cell receptor Valpha spectratype analysis of a CD4-mediated T-cell response against minor histocompatibility antigens involved in severe graft-versus-host disease. Biol Blood Marrow Transplant. 2006;12:818-27 pubmed
    ..These results provide further evidence that a restricted repertoire of T cell specificities, presumably recognizing a correspondingly low number of miHA, is sufficient for the induction of severe GVHD. ..
  39. Bas A, Forsberg G, Sjöberg V, Hammarstrom S, Hernell O, Hammarstrom M. Aberrant extrathymic T cell receptor gene rearrangement in the small intestinal mucosa: a risk factor for coeliac disease?. Gut. 2009;58:189-95 pubmed publisher
    ..This is an inherent feature, which probably plays a pivotal role in the failure to efficiently downregulate the T cell response to gluten. ..
  40. Dulude G, Cheynier R, Gauchat D, Abdallah A, Kettaf N, SEKALY R, et al. The magnitude of thymic output is genetically determined through controlled intrathymic precursor T cell proliferation. J Immunol. 2008;181:7818-24 pubmed
    ..Our results provide the first demonstration of the genetic regulation of thymic output. ..
  41. Forestier C, Molano A, Im J, Dutronc Y, Diamond B, Davidson A, et al. Expansion and hyperactivity of CD1d-restricted NKT cells during the progression of systemic lupus erythematosus in (New Zealand Black x New Zealand White)F1 mice. J Immunol. 2005;175:763-70 pubmed
  42. Serwold T, Hochedlinger K, Swindle J, HEDGPETH J, Jaenisch R, Weissman I. T-cell receptor-driven lymphomagenesis in mice derived from a reprogrammed T cell. Proc Natl Acad Sci U S A. 2010;107:18939-43 pubmed publisher
  43. Huang C, Kanagawa O. Impact of early expression of TCR alpha chain on thymocyte development. Eur J Immunol. 2004;34:1532-41 pubmed
  44. Wilson D. GAD-about BDC2.5: peptides that stimulate BDC2.5 T cells and inhibit IDDM. J Autoimmun. 2003;20:199-201 pubmed
  45. Hagihara M, Gansuvd B, Ueda Y, Tsuchiya T, Masui A, Tazume K, et al. Killing activity of human umbilical cord blood-derived TCRValpha24(+) NKT cells against normal and malignant hematological cells in vitro: a comparative study with NK cells or OKT3 activated T lymphocytes or with adult peripheral blood NKT cells. Cancer Immunol Immunother. 2002;51:1-8 pubmed
    ..Basically, those cells might not be contributing to the immune surveillance of hematological malignancies, as shown by a relatively low cytotoxicity against malignant cells, together with the quite strong killing against auto-DCs. ..
  46. Saitou M, Sadamori N, Isobe M. Identification of an aberrant type of rearrangement in the T-cell receptor alpha/delta locus in adult T-cell leukemia. J Hum Genet. 2001;46:706-11 pubmed
    ..1-J40 rearrangement. These findings are the first direct demonstration that successive rearrangements with hybrid joints occur on the same chromosome in the human TCR alpha locus. ..
  47. Vasseur F, Le Campion A, Penit C. Scheduled kinetics of cell proliferation and phenotypic changes during immature thymocyte generation. Eur J Immunol. 2001;31:3038-47 pubmed
    ..These data show that precursor thymocytes undergo two independent waves of expansion, and that the second wave is restricted to cells capable of pre-TCR expression. ..
  48. 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) ..
  49. Mancini S, Candéias S, Fehling H, von Boehmer H, Jouvin Marche E, Marche P. TCR alpha-chain repertoire in pTalpha-deficient mice is diverse and developmentally regulated: implications for pre-TCR functions and TCRA gene rearrangement. J Immunol. 1999;163:6053-9 pubmed
  50. Sim B, Wung J, Gascoigne N. Polymorphism within a TCRAV family influences the repertoire through class I/II restriction. J Immunol. 1998;160:1204-11 pubmed
  51. Ramiro A, Trigueros C, Marquez C, San Millan J, Toribio M. Regulation of pre-T cell receptor (pT alpha-TCR beta) gene expression during human thymic development. J Exp Med. 1996;184:519-30 pubmed
  52. Shores E, Tran T, Grinberg A, Sommers C, Shen H, Love P. Role of the multiple T cell receptor (TCR)-zeta chain signaling motifs in selection of the T cell repertoire. J Exp Med. 1997;185:893-900 pubmed
    ..These results reveal a role for multiple TCR ITAMs in thymocyte selection and identify a function for TCR signal amplification in formation of the T cell repertoire. ..
  53. Lauzurica P, Bragado R, Lopez D, Galocha B, Lopez de Castro J. Asymmetric selection of T cell antigen receptor alpha- and beta-chains in HLA-B27 alloreactivity. J Immunol. 1992;148:3624-30 pubmed
    ..They suggest recognition of multiple peptides and involvement of beta-chain junctional regions in recognizing shared motifs among some of these peptides. ..