Genomes and Genes
alpha chain t cell antigen receptor gene rearrangement
Summary: Ordered rearrangement of T-cell variable gene regions coding for the alpha-chain of antigen receptors.
- 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. ..
- 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
- 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
- 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. ..
- 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. ..
- 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. ..
- 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
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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
- 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. ..
- 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
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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
- 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. ..
- 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. ..
- 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. ..
- 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
- Huang C, Kanagawa O. Impact of early expression of TCR alpha chain on thymocyte development. Eur J Immunol. 2004;34:1532-41 pubmed
- Wilson D. GAD-about BDC2.5: peptides that stimulate BDC2.5 T cells and inhibit IDDM. J Autoimmun. 2003;20:199-201 pubmed
- 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. ..
- 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. ..
- 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. ..
- 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) ..
- 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
- 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
- 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
- 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. ..
- 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. ..