t cell receptor alpha genes


Summary: DNA sequences encoding the alpha chain of the T-cell receptor. The genomic organization of the TcR alpha genes is essentially the same in all species and is similar to the organization of Ig genes.

Top Publications

  1. Cui J, Shin T, Kawano T, Sato H, Kondo E, Toura I, et al. Requirement for Valpha14 NKT cells in IL-12-mediated rejection of tumors. Science. 1997;278:1623-6 pubmed
  2. Aifantis I, Buer J, von Boehmer H, Azogui O. Essential role of the pre-T cell receptor in allelic exclusion of the T cell receptor beta locus. Immunity. 1997;7:601-7 pubmed
    ..Thus, the pre-TCR-independent suppression of rearrangement by TCR beta transgenes represents a transgene artifact, whereas under physiological conditions the pre-TCR is essential for allelic exclusion. ..
  3. 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. ..
  4. Ronet C, Mempel M, Thieblemont N, Lehuen A, Kourilsky P, Gachelin G. Role of the complementarity-determining region 3 (CDR3) of the TCR-beta chains associated with the V alpha 14 semi-invariant TCR alpha-chain in the selection of CD4+ NK T Cells. J Immunol. 2001;166:1755-62 pubmed
    ..The structure of the TCR of NK T cells thus reflects the affinity for the CD1d molecule rather than a structural constraint leading to the association of the invariant alpha-chain with a distinctive subset of Vbeta segment. ..
  5. 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. ..
  6. Bassing C, Tillman R, Woodman B, Canty D, Monroe R, Sleckman B, et al. T cell receptor (TCR) alpha/delta locus enhancer identity and position are critical for the assembly of TCR delta and alpha variable region genes. Proc Natl Acad Sci U S A. 2003;100:2598-603 pubmed
    ..Therefore, unlike E alpha, E delta lacks ability to function over the large intervening TCR alpha locus and or E delta function requires proximity to additional upstream element(s) to promote TCR delta accessibility. ..
  7. Sim B, Holmberg K, Sidobre S, Naidenko O, Niederberger N, Marine S, et al. Surprisingly minor influence of TRAV11 (Valpha14) polymorphism on NK T-receptor mCD1/alpha-galactosylceramide binding kinetics. Immunogenetics. 2003;54:874-83 pubmed
    ..These differences are minor compared with differences between agonist and antagonist ligands in other TCR systems, suggesting that it is unlikely that TCR polymorphism explains the defect in NK T cells in the autoimmune mouse strains. ..
  8. Zhong X, Krangel M. Enhancer-blocking activity within the DNase I hypersensitive site 2 to 6 region between the TCR alpha and Dad1 genes. J Immunol. 1999;163:295-300 pubmed
    ..We propose that HS2-6 primarily functions as an insulator or boundary element that may be critical for the autonomous regulation of the TCR alpha and Dad1 genes. ..
  9. Eberl G, Lees R, Smiley S, Taniguchi M, Grusby M, MacDonald H. Tissue-specific segregation of CD1d-dependent and CD1d-independent NK T cells. J Immunol. 1999;162:6410-9 pubmed
    ..Collectively, our data suggest that recognition of tissue-specific ligands by the TCR controls localization and activation of NKT cells. ..

More Information


  1. Kikkert M, Doolman R, Dai M, Avner R, Hassink G, van Voorden S, et al. Human HRD1 is an E3 ubiquitin ligase involved in degradation of proteins from the endoplasmic reticulum. J Biol Chem. 2004;279:3525-34 pubmed
    ..Additionally we show that human HRD1 is involved in the elimination of two model ER-associated degradation substrates, TCR-alpha and CD3-delta. ..
  2. 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
  3. Cantu C, Benlagha K, Savage P, Bendelac A, Teyton L. The paradox of immune molecular recognition of alpha-galactosylceramide: low affinity, low specificity for CD1d, high affinity for alpha beta TCRs. J Immunol. 2003;170:4673-82 pubmed
    ..This suggests that there is less accommodation made by this TCR in recognizing alpha-galactosylceramide, and it can be assumed that the most rigid part of the Ag, the sugar moiety, is critical in the interaction. ..
  4. Bosc N, Lefranc M. The mouse (Mus musculus) T cell receptor alpha (TRA) and delta (TRD) variable genes. Dev Comp Immunol. 2003;27:465-97 pubmed
    ..The international ImMunoGeneTics information system (http://imgt.cines.fr) created by Marie-Paule Lefranc, Université Montpellier II, CNRS, France. ..
  5. 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. ..
  6. 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
  7. Fries R, Ewald D, Thaller G, Buitkamp J. Assessment of the nucleotide sequence variability in the bovine T-cell receptor alpha delta joining gene region. Anim Biotechnol. 2001;12:29-49 pubmed
    ..Our study demonstrates that the systematic search of single nucleotide polymorphisms (SNPs) is useful for analysing all aspects of variability of a given genomic region. ..
  8. Capone M, Cantarella D, Schumann J, Naidenko O, Garavaglia C, Beermann F, et al. Human invariant V alpha 24-J alpha Q TCR supports the development of CD1d-dependent NK1.1+ and NK1.1- T cells in transgenic mice. J Immunol. 2003;170:2390-8 pubmed
    ..NKT cells. Thus, human inv. V alpha 24 TCR-expressing mice are a valuable model to study different aspects of the inv. NKT cell subset. ..
  9. Kobayashi M, Jasinski J, Liu E, Li M, Miao D, Zhang L, et al. Conserved T cell receptor alpha-chain induces insulin autoantibodies. Proc Natl Acad Sci U S A. 2008;105:10090-4 pubmed publisher
    ..We suggest that a major part of the mystery as to why islet autoimmunity develops relates to recognition of a primary insulin peptide by a conserved alpha chain T cell receptor. ..
  10. Ueno T, Tomiyama H, Fujiwara M, Oka S, Takiguchi M. Functionally impaired HIV-specific CD8 T cells show high affinity TCR-ligand interactions. J Immunol. 2004;173:5451-7 pubmed
    ..Taken together, these data indicate that impaired responsiveness of T cells toward HIV-infected cells can occur at the level of TCR-ligand interactions, providing us further insight into the immune evasion mechanisms by HIV. ..
  11. Hori S, Haury M, Lafaille J, Demengeot J, Coutinho A. Peripheral expansion of thymus-derived regulatory cells in anti-myelin basic protein T cell receptor transgenic mice. Eur J Immunol. 2002;32:3729-35 pubmed
    ..These observations thus exclude peripheral differentiation of Treg in this particular system, and indicate that expansion of thymically committed cells ensures the maintenance of the peripheral Treg pool in the adult. ..
  12. Mantovani S, Palermo B, Garbelli S, Campanelli R, Robustelli Della Cuna G, Gennari R, et al. Dominant TCR-alpha requirements for a self antigen recognition in humans. J Immunol. 2002;169:6253-60 pubmed
    ..Our data demonstrate a dominant function of TCRAV2 segment in forming the TCR repertoire specific for the human self Ag Melan-A/MART-1 and support the view that Ag recognition is mediated predominantly by TCR-alpha. ..
  13. de Yebenes V, Carrasco Y, Ramiro A, Toribio M. Identification of a myeloid intrathymic pathway of dendritic cell development marked by expression of the granulocyte macrophage-colony-stimulating factor receptor. Blood. 2002;99:2948-56 pubmed
  14. Torres Nagel N, Mehling B, LeRolle A, Joly E, Hunig T. Genetic control of peripheral TCRAV usage by representation in the preselection repertoire and MHC allele-specific overselection. Int Immunol. 2001;13:63-73 pubmed
  15. Corcoran L, Ferrero I, Vremec D, Lucas K, Waithman J, O Keeffe M, et al. The lymphoid past of mouse plasmacytoid cells and thymic dendritic cells. J Immunol. 2003;170:4926-32 pubmed
    ..Therefore, many plasmacytoid pre-DC and thymic CD8(+) DC have shared early steps of development with the lymphoid lineages, and differ in origin from conventional peripheral DC. ..
  16. Prell C, Konstantopoulos N, Heinzelmann B, Frankenberger B, Reinhardt D, Schendel D, et al. Frequency of Valpha24+CD161+ natural killer T cells and invariant TCRAV24-AJ18 transcripts in atopic and non-atopic individuals. Immunobiology. 2003;208:367-80 pubmed
    ..If NKT cells contribute to development of type I allergies they must do so at earlier times or in other locations. ..
  17. 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
  18. Junta C, Passos G. Emergence of TCR alpha/beta V(D)J recombination and transcription during ontogeny of inbred mouse strains. Mol Cell Biochem. 1998;187:67-72 pubmed
    ..The transcriptions of these loci followed respective recombinations and we detected an early germline transcript before TCR beta locus recombination in the CBA strain. ..
  19. Vaitaitis G, Poulin M, Sanderson R, Haskins K, Wagner D. Cutting edge: CD40-induced expression of recombination activating gene (RAG) 1 and RAG2: a mechanism for the generation of autoaggressive T cells in the periphery. J Immunol. 2003;170:3455-9 pubmed
    ..Therefore, CD40-regulated expression of RAG1 and RAG2 in peripheral T cells may constitute a novel pathway for the generation of autoaggressive T cells. ..
  20. 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
  21. Lacorazza H, Nikolich Zugich J. Exclusion and inclusion of TCR alpha proteins during T cell development in TCR-transgenic and normal mice. J Immunol. 2004;173:5591-600 pubmed
    ..In searching for the mechanism(s) governing this selective TCRalpha down-regulation, we present evidence for the role of protein tyrosine kinase signaling and coreceptor involvement. This mechanism may be operating in normal thymocytes. ..
  22. Smyth M, Thia K, Street S, Cretney E, Trapani J, Taniguchi M, et al. Differential tumor surveillance by natural killer (NK) and NKT cells. J Exp Med. 2000;191:661-8 pubmed
    ..This is the first description of an antitumor function for NKT cells in the absence of exogenously administered potent stimulators such as IL-12 or alpha-galactosylceramide. ..
  23. 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
  24. Brawley J, Concannon P. Complementarity-determining region 1 sequence requirements drive limited V alpha usage in response to influenza hemagglutinin 307-319 peptide. J Immunol. 2002;168:3894-901 pubmed
    ..This system for mutation and selection of TCRs in vitro may be of use in engineering T cells with defined specificities for therapeutic applications. ..
  25. Blander J, Sant Angelo D, Bottomly K, Janeway C. Alteration at a single amino acid residue in the T cell receptor alpha chain complementarity determining region 2 changes the differentiation of naive CD4 T cells in response to antigen from T helper cell type 1 (Th1) to Th2. J Exp Med. 2000;191:2065-74 pubmed
    ..We conclude from these data that a mutation in the TCR at a key position that contacts major histocompatibility complex-bound peptide is associated with a shift in T cell differentiation from Th1 to Th2. ..
  26. Peterfalvi A, Gomori E, Magyarlaki T, Pal J, Banati M, Javorhazy A, et al. Invariant Valpha7.2-Jalpha33 TCR is expressed in human kidney and brain tumors indicating infiltration by mucosal-associated invariant T (MAIT) cells. Int Immunol. 2008;20:1517-25 pubmed publisher
    ..Our data imply that a CD56- subset of MAIT cells may participate in tumor immune responses similarly to NKT cells. ..
  27. Mempel M, Ronet C, Suarez F, Gilleron M, Puzo G, Van Kaer L, et al. Natural killer T cells restricted by the monomorphic MHC class 1b CD1d1 molecules behave like inflammatory cells. J Immunol. 2002;168:365-71 pubmed
  28. Kranz D, Manning T, Rund L, Cho B, Gruber M, Roy E. Targeting tumor cells with bispecific antibodies and T cells. J Control Release. 1998;53:77-84 pubmed
    ..This transgenic mouse model should now allow the evaluation and optimization of bispecific agents that can redirect a patient's own T cell response. ..
  29. Brabb T, Rubicz R, Mannikko V, Goverman J. Separately expressed T cell receptor alpha and beta chain transgenes exert opposite effects on T cell differentiation and neoplastic transformation. Eur J Immunol. 1997;27:3039-48 pubmed
    ..Our observations provide a model for understanding T cell differentiation in TCR-transgenic mice. ..
  30. Shimamoto T, Ohyashiki K. Immunosuppressive treatments for myelodysplastic syndromes. Leuk Lymphoma. 2003;44:593-604 pubmed
    ..We have to establish the clinical usefulness of immunosuppressive therapy in MDS patients and simple tools for revealing T-cell mediated myelosuppression in the individual patients for decision-making. ..
  31. Skok J, Gisler R, Novatchkova M, Farmer D, de Laat W, Busslinger M. Reversible contraction by looping of the Tcra and Tcrb loci in rearranging thymocytes. Nat Immunol. 2007;8:378-87 pubmed
    ..Hence, pericentromeric recruitment and locus 'decontraction' seem to contribute to the initiation and maintenance of allelic exclusion at the Tcrb locus. ..
  32. Soriano J, de Cid R, Estivill X, Anto J, Sunyer J, Otero D, et al. Association study of proposed candidate genes/regions in a population of Spanish asthmatics. Eur J Epidemiol. 2000;16:745-50 pubmed
    ..No association could be observed in this sample of Spanish asthmatics with the genes/regions studied. ..
  33. 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. ..
  34. Santoso B, Ortiz B, Winoto A. Control of organ-specific demethylation by an element of the T-cell receptor-alpha locus control region. J Biol Chem. 2000;275:1952-8 pubmed
    ..Thus, elements of an LCR can control tissue-specific DNA methylation patterns both in transgenes and inside its native locus. ..
  35. Daubenberger C, Nickel B, Ciatto C, Grutter M, Pöltl Frank F, Rossi L, et al. Amino acid dimorphism and parasite immune evasion: cellular immune responses to a promiscuous epitope of Plasmodium falciparum merozoite surface protein 1 displaying dimorphic amino acid polymorphism are highly constrained. Eur J Immunol. 2002;32:3667-77 pubmed
    ..Lack of productive triggering of the TCR by MHC/variant peptide ligand complexes thus seems to be the characteristic feature of parasite immune evasion associated with antigen dimorphism. ..
  36. Naeher D, Luescher I, Palmer E. A role for the alpha-chain connecting peptide motif in mediating TCR-CD8 cooperation. J Immunol. 2002;169:2964-70 pubmed
    ..The experiments presented in this work show that alpha-CPM-deficient TCRs fail to cooperate with CD8 to enhance ligand binding and functional responses. ..
  37. Laouini D, Casrouge A, Dalle S, Lemonnier F, Kourilsky P, Kanellopoulos J. V beta T cell repertoire of CD8+ splenocytes selected on nonpolymorphic MHC class I molecules. J Immunol. 2000;165:6381-6 pubmed
    ..This observation implies that BV diversity is positively correlated with the number of CD8(+) cells, even when the number of CD8(+) splenocytes is dramatically reduced (90% in the double knockout mice). ..
  38. Magdinier F, Yusufzai T, Felsenfeld G. Both CTCF-dependent and -independent insulators are found between the mouse T cell receptor alpha and Dad1 genes. J Biol Chem. 2004;279:25381-9 pubmed
    ..However, other regions within the 6-kb element that also can block enhancers clearly do not harbor CTCF sites and thus must reflect the presence of a previously undetected and distinct vertebrate insulator activity. ..
  39. Englund P, Wahlstrom J, Fathi M, Rasmussen E, Grunewald J, Tornling G, et al. Restricted T cell receptor BV gene usage in the lungs and muscles of patients with idiopathic inflammatory myopathies. Arthritis Rheum. 2007;56:372-83 pubmed
    ..e., lung and muscle). The occurrence of shared TCR gene segment usage in muscle and lungs could suggest common target antigens in these organs. ..
  40. Bhandoola A, Dolnick B, Fayad N, Nussenzweig A, Singer A. Immature thymocytes undergoing receptor rearrangements are resistant to an Atm-dependent death pathway activated in mature T cells by double-stranded DNA breaks. J Exp Med. 2000;192:891-7 pubmed
    ..It is likely that the unique ability of immature thymocytes to survive DNA-damaging intercalating agents reflects their tolerance of double-stranded DNA breaks that occur normally during antigen receptor gene rearrangements. ..
  41. 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 publisher
    ..Collectively, these findings suggest that invariant Valpha19 TCR(+) cells have the potential to participate in the regulation of inflammatory autoimmunity by producing T(h)2-biased cytokines in certain circumstances. ..
  42. Matsuki Y, Zhang H, Hsu H, Yang P, Zhou T, Dodd C, et al. Different role of Apaf-1 in positive selection, negative selection and death by neglect in foetal thymic organ culture. Scand J Immunol. 2002;56:174-84 pubmed
    ..Our data suggest that Apaf-1 is not involved in positive selection or death by neglect, but may have a partial role in negative selection during early thymic T-cell development. ..
  43. Abarrategui I, Krangel M. Regulation of T cell receptor-alpha gene recombination by transcription. Nat Immunol. 2006;7:1109-15 pubmed
    ..These influences promote an ordered progression of Tcra locus recombination events and selection of a robust Tcra repertoire. ..
  44. Petersson K, Ivars F. Early TCR alpha beta expression promotes maturation of T cells expressing Fc epsilon RI gamma containing TCR/CD3 complexes. J Immunol. 2001;166:6616-24 pubmed
  45. Schnell S, Démollière C, van den Berk P, Kirberg J, Jacobs H. Constitutive expression of the pre-TCR enables development of mature T cells. Int Immunol. 2006;18:911-20 pubmed
    ..Lymphopenia-driven proliferation of these betaT cells is similar to that of conventional alphabetaT cells. Furthermore, betaT cells proliferated and acquired effector function upon stimulation with allogeneic MHC. ..
  46. Huang C, Sleckman B, Kanagawa O. Revision of T cell receptor {alpha} chain genes is required for normal T lymphocyte development. Proc Natl Acad Sci U S A. 2005;102:14356-61 pubmed
    ..Together, these findings demonstrate that normal T cell development relies on the ability of developing thymocytes to revise their TCRalpha chain genes. ..
  47. Gadue P, Yin L, Jain S, Stein P. Restoration of NK T cell development in fyn-mutant mice by a TCR reveals a requirement for Fyn during early NK T cell ontogeny. J Immunol. 2004;172:6093-100 pubmed
  48. Schmid C, Stienekemeier M, Oehen S, Bootz F, Zielasek J, Gold R, et al. Immune deficiency in mouse models for inherited peripheral neuropathies leads to improved myelin maintenance. J Neurosci. 2000;20:729-35 pubmed
    ..We hypothesize that autoreactive immune cells can significantly foster the demyelinating phenotype of mice with a primarily genetically based peripheral neuropathy. ..
  49. Chuzhanova N, Abeysinghe S, Krawczak M, Cooper D. Translocation and gross deletion breakpoints in human inherited disease and cancer II: Potential involvement of repetitive sequence elements in secondary structure formation between DNA ends. Hum Mutat. 2003;22:245-51 pubmed
    ..These findings extend our understanding of illegitimate recombination by highlighting the importance of secondary structure formation between single-stranded DNA ends at breakpoint junctions. ..
  50. Bobisse S, Rondina M, Merlo A, Tisato V, Mandruzzato S, Amendola M, et al. Reprogramming T lymphocytes for melanoma adoptive immunotherapy by T-cell receptor gene transfer with lentiviral vectors. Cancer Res. 2009;69:9385-94 pubmed publisher
    ..Overall, our results indicate that lentiviral vectors represent a valid tool for stable and high-intensity expression of transgenic TCR and support clinical exploitation of this approach for therapeutic application. ..
  51. Haynes M, Wu G. Gene discovery at the human T-cell receptor alpha/delta locus. Immunogenetics. 2007;59:109-21 pubmed
    ..The identification of conserved putative serine phosphorylation sites provide evidence of their possible role(s) in signal transduction events involved in B cell development and differentiation. ..
  52. Haag E, Ackerman A. Intraspecific variation in fem-3 and tra-2, two rapidly coevolving nematode sex-determining genes. Gene. 2005;349:35-42 pubmed
    ..The FEM-3-binding domain of TRA-2 is less polymorphic than FEM-3. Amino acids neither polymorphic nor conserved between species are candidates for residues mediating species-specific interaction of FEM-3 with its binding partners. ..
  53. Bonfigli S, Doro M, Fozza C, Derudas D, Dore F, Longinotti M. T-cell receptor repertoire in healthy Sardinian subjects. Hum Immunol. 2003;64:689-95 pubmed
    ..Finally, the profound perturbations evidenced in the CD8+ T cell subpopulation could be related to a different response to the antigenic stimulation between CD8+ and CD4+ T lymphocytes. ..