Genomes and Genes
Gene Symbol: Tcra
Description: T cell receptor alpha chain
Alias: Tcralpha, Tcr alpha
- Niederberger N, Holmberg K, Alam S, Sakati W, Naramura M, Gu H, et al. Allelic exclusion of the TCR alpha-chain is an active process requiring TCR-mediated signaling and c-Cbl. J Immunol. 2003;170:4557-63 pubmedPhenotypic allelic exclusion at the TCRalpha locus is developmentally regulated in thymocytes. Many immature thymocytes express two cell surface alpha-chain species...
- Hsieh C, Zheng Y, Liang Y, Fontenot J, Rudensky A. An intersection between the self-reactive regulatory and nonregulatory T cell receptor repertoires. Nat Immunol. 2006;7:401-10 pubmed..Our analyses suggest that T(reg) cells and potentially pathogenic autoimmune T cells use overlapping pools of self-reactive TCRs. ..
- Faulkner L, Cooper A, Fantino C, Altmann D, Sriskandan S. The mechanism of superantigen-mediated toxic shock: not a simple Th1 cytokine storm. J Immunol. 2005;175:6870-7 pubmed..Our results demonstrate unequivocally that TCRalphabeta T cells are critical for lethality in toxic shock but it is the early TNF-alpha response and not the later cytokine surge that mediates lethal shock. ..
- McCaughtry T, Baldwin T, Wilken M, Hogquist K. Clonal deletion of thymocytes can occur in the cortex with no involvement of the medulla. J Exp Med. 2008;205:2575-84 pubmed publisher..Rather, thymocytes undergoing clonal deletion were preferentially associated with rare CD11c(+) cortical dendritic cells, and elimination of such cells impaired deletion. ..
- Golub R, Huang C, Kanagawa O, Wu G. Valpha gene replacement in a TCRalpha knock-in mouse. Eur J Immunol. 2001;31:2919-25 pubmedUsing a TCRalpha chain knock-in mouse, we demonstrate that V-gene replacement can operate in the T cell receptor alpha locus...
- Sharara L, Andersson A, Guy Grand D, Fischer A, DiSanto J. Deregulated TCR alpha beta T cell population provokes extramedullary hematopoiesis in mice deficient in the common gamma chain. Eur J Immunol. 1997;27:990-8 pubmed..Peripheral TCR alpha beta T cells from gamma c- mice were characterized by an activated phenotype (CD62Llo, CD44hi, CD69hi) and ..
- 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..of the alphabeta and gammadelta T cell lineages is dependent upon the rearrangement and expression of the TCRalpha and beta or gamma and delta genes, respectively...
- Inoue K, Wakao H, Ogonuki N, Miki H, Seino K, Nambu Wakao R, et al. Generation of cloned mice by direct nuclear transfer from natural killer T cells. Curr Biol. 2005;15:1114-8 pubmed
- 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..The introduced TCR alpha chain gene is expressed in a majority of CD3 positive and CD4 CD8 double-negative immature thymocytes...
- Pacholczyk R, Kern J, Singh N, Iwashima M, Kraj P, Ignatowicz L. Nonself-antigens are the cognate specificities of Foxp3+ regulatory T cells. Immunity. 2007;27:493-504 pubmed..Our results show that high-affinity, autoreactive TCRs are rare on all CD4+ T cells and suggest that selecting self-peptide is different from the peptide that activates the same regulatory T cells in the periphery. ..
- Sun G, Liu X, Mercado P, Jenkinson S, Kypriotou M, Feigenbaum L, et al. The zinc finger protein cKrox directs CD4 lineage differentiation during intrathymic T cell positive selection. Nat Immunol. 2005;6:373-81 pubmed..CD4 lineage differentiation mediated by cKrox required its N-terminal BTB (bric-a-brac, tramtrack, broad complex) domain. These findings identify cKrox as a chief CD4 differentiation factor during positive selection. ..
- Pennington D, Silva Santos B, Shires J, Theodoridis E, Pollitt C, Wise E, et al. The inter-relatedness and interdependence of mouse T cell receptor gammadelta+ and alphabeta+ cells. Nat Immunol. 2003;4:991-8 pubmed..Thus, normal gammadelta cell development is dependent on the development of conventional alphabeta T cells. ..
- Polic B, Kunkel D, Scheffold A, Rajewsky K. How alpha beta T cells deal with induced TCR alpha ablation. Proc Natl Acad Sci U S A. 2001;98:8744-9 pubmed
- McGuire M, Suthipinijtham P, Gascoigne N. The mouse Supt16h/Fact140 gene, encoding part of the FACT chromatin transcription complex, maps close to Tcra and is highly expressed in thymus. Mamm Genome. 2001;12:664-7 pubmed
- Wong J, Obst R, Correia Neves M, Losyev G, Mathis D, Benoist C. Adaptation of TCR repertoires to self-peptides in regulatory and nonregulatory CD4+ T cells. J Immunol. 2007;178:7032-41 pubmed..of the "Limited" (LTD) mouse, which has a restricted TCR repertoire with a fixed TCRbeta chain and a TCRalpha chain minilocus...
- Boyton R, Zaccai N, Jones E, Altmann D. CD4 T cells selected by antigen under Th2 polarizing conditions favor an elongated TCR alpha chain complementarity-determining region 3. J Immunol. 2002;168:1018-27 pubmed..This trend was confirmed by analyzing TCRalpha transcripts from Th1 and Th2 polarized, bulk populations...
- Kouskoff V, Korganow A, Duchatelle V, Degott C, Benoist C, Mathis D. Organ-specific disease provoked by systemic autoimmunity. Cell. 1996;87:811-22 pubmed..We suggest that human RA develops by an analogous mechanism. ..
- Shimamura M, Huang Y, Okamoto N, Suzuki N, Yasuoka J, Morita K, et al. Modulation of Valpha19 NKT cell immune responses by alpha-mannosyl ceramide derivatives consisting of a series of modified sphingosines. Eur J Immunol. 2007;37:1836-44 pubmed..Thus, these alpha-ManCer derivatives are likely to be useful in immunotherapy for either Th1 or Th2 excess autoimmune diseases, modulating the function of Valpha19 NKT cells. ..
- dos Santos N, Rickman D, de Reynies A, Cormier F, Williame M, Blanchard C, et al. Pre-TCR expression cooperates with TEL-JAK2 to transform immature thymocytes and induce T-cell leukemia. Blood. 2007;109:3972-81 pubmed..Although not affecting leukemia incidence and mouse survival, TCRalphabeta expression was shown to facilitate leukemic cell expansion in secondary lymphoid organs. ..
- Mizoguchi A, Mizoguchi E, Bhan A. The critical role of interleukin 4 but not interferon gamma in the pathogenesis of colitis in T-cell receptor alpha mutant mice. Gastroenterology. 1999;116:320-6 pubmedT-cell receptor alpha mutant (TCRalpha-/-) mice spontaneously develop colitis resembling ulcerative colitis (UC)...
- Wakao H, Kawamoto H, Sakata S, Inoue K, Ogura A, Wakao R, et al. A novel mouse model for invariant NKT cell study. J Immunol. 2007;179:3888-95 pubmed..These mice will be useful for the study on the development of iNKT cells as well as on their functions in the immune system. ..
- Luhder F, Katz J, Benoist C, Mathis D. Major histocompatibility complex class II molecules can protect from diabetes by positively selecting T cells with additional specificities. J Exp Med. 1998;187:379-87 pubmed..in CD4(+) cells displaying the transgene-encoded TCR and an increase in cells expressing endogenously encoded TCR alpha-chains...
- Kitano M, Moriyama S, Ando Y, Hikida M, Mori Y, Kurosaki T, et al. Bcl6 protein expression shapes pre-germinal center B cell dynamics and follicular helper T cell heterogeneity. Immunity. 2011;34:961-72 pubmed publisher..These results clarify the role of Bcl6 in pre-GC B cell dynamics and highlight the modulation of Bcl6 expression in Tfh cells that persist in the late phase of the antibody response. ..
- Malissen B, Malissen M. Functions of TCR and pre-TCR subunits: lessons from gene ablation. Curr Opin Immunol. 1996;8:383-93 pubmed..By activating intracellular effectors, the CD3 subunits probably modulate gene expression profiles and drive the maturing alpha beta T cells through a precise developmental sequence. ..
- Gaszewska Mastalarz A, Muranski P, Chmielowski B, Kraj P, Ignatowicz L. Altered selection of CD4+ T cells by class II MHC bound with dominant and low abundance self-peptides. J Immunol. 2000;165:6099-106 pubmed
- Coles M, Raulet D. NK1.1+ T cells in the liver arise in the thymus and are selected by interactions with class I molecules on CD4+CD8+ cells. J Immunol. 2000;164:2412-8 pubmed..We show that the class I+ (CD1d+) cell type necessary to select NK1.1+ T cells can originate from TCRalpha-/- precursors but not from TCRbeta-/- precursors, indicating that the selecting cell is a CD4+CD8+ thymocyte...
- Okamoto N, Kanie O, Huang Y, Fujii R, Watanabe H, Shimamura M. Synthetic alpha-mannosyl ceramide as a potent stimulant for an NKT cell repertoire bearing the invariant Valpha19-Jalpha26 TCR alpha chain. Chem Biol. 2005;12:677-83 pubmedA NKT cell repertoire is characterized by the expression of the Valpha19-Jalpha26 invariant TCR alpha chain (Valpha19 NKT cell)...
- Shimamura M, Huang Y, Kobayashi M, Goji H. Altered production of immunoregulatory cytokines by invariant Valpha19 TCR-bearing cells dependent on the duration and intensity of TCR engagement. Int Immunol. 2009;21:179-85 pubmed publisherCells bearing invariant Valpha19-Jalpha33 TCR alpha chains are believed to participate in the regulation of inflammatory autoimmune diseases...
- Wong F, Siew L, Scott G, Thomas I, Chapman S, Viret C, et al. Activation of insulin-reactive CD8 T-cells for development of autoimmune diabetes. Diabetes. 2009;58:1156-64 pubmed publisher..scid mice. Autoimmune CD8 T-cells responding to a low-affinity insulin B-chain peptide escape from thymic negative selection and require activation in vivo to cause diabetes. ..
- Feuerer M, Herrero L, Cipolletta D, Naaz A, Wong J, Nayer A, et al. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med. 2009;15:930-9 pubmed publisher..These observations suggest that harnessing the anti-inflammatory properties of T(reg) cells to inhibit elements of the metabolic syndrome may have therapeutic potential...
- Laird R, Laky K, Hayes S. Unexpected role for the B cell-specific Src family kinase B lymphoid kinase in the development of IL-17-producing ?? T cells. J Immunol. 2010;185:6518-27 pubmed publisher..Furthermore, Blk is expressed in lymphoid precursors and, in this capacity, plays a role in regulating thymus cellularity during ontogeny. ..
- Correia Neves M, Waltzinger C, Mathis D, Benoist C. The shaping of the T cell repertoire. Immunity. 2001;14:21-32 pubmedBy combining a TCRbeta transgene with a TCRalpha minilocus comprised of a single V and two J gene segments, we engineered a mouse line exhibiting ample but focused TCR diversity, restricted to CDR3alpha...
- Serreze D, Johnson E, Chapman H, Graser R, Marron M, DiLorenzo T, et al. Autoreactive diabetogenic T-cells in NOD mice can efficiently expand from a greatly reduced precursor pool. Diabetes. 2001;50:1992-2000 pubmed..This might allow diabetogenic T-cells in NOD mice to undergo an efficient expansion before encountering antigen, which would represent an important and previously unconsidered aspect of pathogenesis. ..
- Baldwin T, Sandau M, Jameson S, Hogquist K. The timing of TCR alpha expression critically influences T cell development and selection. J Exp Med. 2005;202:111-21 pubmed..Collectively, these data establish the importance of proper timing of TCR expression in thymic development and selection and emphasize the need to use models that most accurately reflect the physiologic process. ..
- 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..transgenic mouse model in which self-reactive thymocytes could edit their TCR by secondary recombination at the TCR alpha locus...
- 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 pubmedWe have used gene targeted mutational approaches to assess the role of the T cell receptor alpha (TCR alpha) enhancer (E alpha) in the control of TCR alpha and TCR delta gene rearrangement and expression...
- Arnold C, Campbell D, Lipp M, Butcher E. The germinal center response is impaired in the absence of T cell-expressed CXCR5. Eur J Immunol. 2007;37:100-9 pubmed
- Haks M, Belkowski S, Ciofani M, Rhodes M, Lefebvre J, Trop S, et al. Low activation threshold as a mechanism for ligand-independent signaling in pre-T cells. J Immunol. 2003;170:2853-61 pubmed..We report that ligand-independent signaling is not a unique capability of the pre-TCR complex. Indeed, the TCR alpha subunit restores development of pT alpha-deficient thymocytes to the CD4(+)CD8(+) stage even in the absence of ..
- Mizoguchi A, Mizoguchi E, Smith R, Preffer F, Bhan A. Suppressive role of B cells in chronic colitis of T cell receptor alpha mutant mice. J Exp Med. 1997;186:1749-56 pubmed..These findings suggest that although B cells are not required for the initiation of colitis, B cells and Igs (autoAbs) can suppress colitis, presumably by affecting the clearance of apoptotic cells. ..
- Ribot J, deBarros A, Mancio Silva L, Pamplona A, Silva Santos B. B7-CD28 costimulatory signals control the survival and proliferation of murine and human ?? T cells via IL-2 production. J Immunol. 2012;189:1202-8 pubmed publisher..Our data collectively show that CD28 signals are required for IL-2-mediated survival and proliferation of both CD27(+) and CD27(-) ?? T cell subsets, thus providing new mechanistic insight for their modulation in disease models. ..
- Fehling H, von Boehmer H. Early alpha beta T cell development in the thymus of normal and genetically altered mice. Curr Opin Immunol. 1997;9:263-75 pubmed..by a pre-TCR complex consisting of a conventional TCR beta chain and a novel transmembrane protein termed pre-TCR alpha (p T alpha chain) which are noncovalently associated with components of CD3...
- Pape K, Taylor J, Maul R, Gearhart P, Jenkins M. Different B cell populations mediate early and late memory during an endogenous immune response. Science. 2011;331:1203-7 pubmed publisher..Thus, we propose that memory relies on swIg(+) cells until they disappear and serum immunoglobulin falls to a low level, in which case memory resides with durable IgM(+) reserves. ..
- Borowski C, Li X, Aifantis I, Gounari F, von Boehmer H. Pre-TCRalpha and TCRalpha are not interchangeable partners of TCRbeta during T lymphocyte development. J Exp Med. 2004;199:607-15 pubmed..Here, we express TCRalpha precisely at the pre-TCR checkpoint, at levels resembling those of endogenous pre-TCRalpha (pTalpha), and in the ..
- Dianda L, Gulbranson Judge A, Pao W, Hayday A, MacLennan I, Owen M. Germinal center formation in mice lacking alpha beta T cells. Eur J Immunol. 1996;26:1603-7 pubmed..However, class-switched antibodies are readily detectable in TCR alpha-deficient mice that congenitally lack alpha beta T cells, including those such as IgG1 that are considered to be ..
- Moon J, Dash P, Oguin T, McClaren J, Chu H, Thomas P, et al. Quantitative impact of thymic selection on Foxp3+ and Foxp3- subsets of self-peptide/MHC class II-specific CD4+ T cells. Proc Natl Acad Sci U S A. 2011;108:14602-7 pubmed publisher..Therefore, thymic selection of self-pMHCII-specific CD4(+) T cells results in incomplete deletion within the normal polyclonal repertoire, especially among regulatory T cells. ..
- Schumann J, Mycko M, Dellabona P, Casorati G, MacDonald H. Cutting edge: influence of the TCR Vbeta domain on the selection of semi-invariant NKT cells by endogenous ligands. J Immunol. 2006;176:2064-8 pubmed..2(+), Valpha14i NKT cells is favored in situations where endogenous ligand concentration or TCRalpha-chain avidity are suboptimal...
- Voehringer D, Reese T, Huang X, Shinkai K, Locksley R. Type 2 immunity is controlled by IL-4/IL-13 expression in hematopoietic non-eosinophil cells of the innate immune system. J Exp Med. 2006;203:1435-46 pubmed..Thus, components of type 2 immunity mediated by IL-4/IL-13 are partitioned between T cell-dependent IgE and an innate non-eosinophil tissue component, suggesting new strategies for interventions in allergic immunity. ..
- Serwold T, Hochedlinger K, Inlay M, Jaenisch R, Weissman I. Early TCR expression and aberrant T cell development in mice with endogenous prerearranged T cell receptor genes. J Immunol. 2007;179:928-38 pubmed
- Eberl G, Fehling H, von Boehmer H, MacDonald H. Absolute requirement for the pre-T cell receptor alpha chain during NK1.1+ TCRalphabeta cell development. Eur J Immunol. 1999;29:1966-71 pubmed..We show here that the development of NKT cells is absolutely dependent on expression of the pre-TCRalpha chain, in marked contrast to conventional T cells which arise in significant numbers even in the absence of a ..
- Martinez R, Zhang N, Thomas S, Nandiwada S, Jenkins M, Binstadt B, et al. Arthritogenic self-reactive CD4+ T cells acquire an FR4hiCD73hi anergic state in the presence of Foxp3+ regulatory T cells. J Immunol. 2012;188:170-81 pubmed publisher..This suggests that autoimmune arthritis develops in the setting of lymphopenia when Foxp3(+)CD4(+) regulatory T cells are insufficient to functionally inactivate all autoreactive CD4(+) T cells that encounter self-Ag. ..
- Au Yeung B, Katzman S, Fowell D. Cutting edge: Itk-dependent signals required for CD4+ T cells to exert, but not gain, Th2 effector function. J Immunol. 2006;176:3895-9 pubmed..We suggest that the liberation of effector function is tightly controlled through qualitative changes in TCR signals, facilitating postdifferentiation regulation of cytokine responses. ..
- Hayes S, Li L, Love P. TCR signal strength influences alphabeta/gammadelta lineage fate. Immunity. 2005;22:583-93 pubmed..These results support a model in which the strength of the TCR signal is a critical determinant in the lineage fate decision. ..
- 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..All the tumors revealed chromosome 14 rearrangements precisely at the T-cell receptoralpha/delta (Tcralpha/delta) locus, suggesting the involvement of V(D)J recombination in these translocations. In addition, 11...
- Wang Q, Malherbe L, Zhang D, Zingler K, Glaichenhaus N, Killeen N. CD4 promotes breadth in the TCR repertoire. J Immunol. 2001;167:4311-20 pubmed..The data thus suggest a key role for CD4 in broadening the TCR repertoire by potentiating productive TCR signaling and clonal expansion in response to the engagement of low-affinity antigenic ligands. ..
- 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..By analyzing TCRalpha rearrangement in orphan nuclear receptor RORgamma-deficient mice, in which the DP lifespan is shorter, and in Bcl-..
- Karnowski A, Chevrier S, Belz G, Mount A, Emslie D, D Costa K, et al. B and T cells collaborate in antiviral responses via IL-6, IL-21, and transcriptional activator and coactivator, Oct2 and OBF-1. J Exp Med. 2012;209:2049-64 pubmed publisher..Finally, the transcriptional activator Oct2 and its cofactor OBF-1 were identified as regulators of Il6 expression in B cells. ..
- Erman B, Feigenbaum L, Coligan J, Singer A. Early TCRalpha expression generates TCRalphagamma complexes that signal the DN-to-DP transition and impair development. Nat Immunol. 2002;3:564-9 pubmed..T cell receptor (TCR) genes undergo ordered rearrangement and expression in the thymus with the result that TCRalpha and TCRgamma proteins are not expressed in the same cell at the same time...