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Gene Review

TRA  -  T cell receptor alpha locus

Homo sapiens

Synonyms: IMD7, TCRA, TCRD, TRA@, TRAC
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Disease relevance of TRA@

  • A small immature subgroup of CD3- T-ALL (n = 5) had both TCRG genes in germline configuration, three of them having also germline TCRD genes [1].
  • Thirty T cell receptor (TCR)gammadelta+ T cell acute lymphoblastic leukemias (T-ALL) were analyzed for their immunophenotype, as well as for the rearrangements and junctional regions of the TCRG and TCRD genes [2].
  • Subsequently, we evaluated, whether heteroduplex PCR analysis of rearranged TCRG and TCRD genes can be used for reliable identification of PCR targets for detection of minimal residual disease (MRD) [3].
  • Application of the new FISH assays to a series of 24 angioimmunoblastic and 12 cutaneous T-cell lymphomas confirmed the cytogenetic evidence of lack of breakpoints in the TCRA/D or TCRB locus [4].
  • Here, we describe the molecular characterization of a novel chromosomal aberration, inv(14)(q11.2q32.31), in a T-ALL sample, involving the recently described BCL11B gene and the TCRD locus [5].

High impact information on TRA@


Chemical compound and disease context of TRA@

  • Between April 1993 and June 1994, 29 patients (pts) with unresectable, locally advanced, or metastatic non-small cell lung cancer were treated with a combination of p.o. trans-retinoic acid (TRA), 150 mg/m2/day, in three divided doses and s.c. IFN-alpha, 3 x 10(6) units/day [9].
  • Twenty-nine chemotherapy-naive patients with primary hepatocellular carcinoma were treated with oral beta-all trans-retinoic acid (retinoic acid, TRA 50 mg/m2 t.i.d.) on a 3-week on/one week off schedule until progression or grade 3 or 4 toxicity [10].
  • The greatest increase in uptake following sepsis was among the gluconeogenic precursor amino acids alanine, glycine, threonine, and serine (CON, 27.0 +/- 4.2 mumol/g liver protein, TRA, 38.8 +/- 8.9 mumol/g liver protein; CLP, 62.8 +/- 6.0 mumol/g liver protein).(ABSTRACT TRUNCATED AT 250 WORDS)[11]
  • These included (i) 14 controls; (ii) 23 patients with Graves' disease who were tested for TRA within 3 months of commencing treatment with carbimazole of which 13 were studied serially; (iii) 5 patients with toxic nodular goitre; (iv) 4 with euthyroid exophthalmos; and (v) 2 neonates of thyrotoxic mothers [12].

Biological context of TRA@


Anatomical context of TRA@

  • We resequenced all 57 variable (V) genes in the human T cell receptor alpha and delta (TRA/TRD) locus in 40 individuals of Northern European, Mexican, African-American and Chinese descent [18].
  • Apparently, some parts of the TCRD (Vdelta2-Ddelta region) and TCRG genes are accessible for recombination not only in T cells, but also in early B-cells and even in nonlymphoid cells if the appropriate transcription factors are present [19].
  • Trans-rearrangements between TCRG and TCRD loci, similar in structure and frequency to those observed previously in human lymphoid tissues, were demonstrated in normal mouse thymus by PCR with crossed V gamma/J delta and V delta/J gamma primer pairs [20].
  • A total of 54 primers was developed (1) to amplify rearrangements of the TCRD, TCRG, and IGK (Kde) genes as well as TAL1 deletions; (2) to sequence the junctional regions and breakpoint fusion regions; and (3) to perform MRD detection in bone marrow or peripheral blood samples during follow-up of ALL patients [21].
  • To determine the sensitivity of heteroduplex analysis with renaturation at 4 degrees C, (c)DNA of T cell malignancies with proven clonal rearrangements was serially diluted in (c)DNA of polyclonal mononuclear peripheral blood cells and amplified using V and C primers (TCRB genes) or V and J primers (TCRG and TCRD genes) [22].

Associations of TRA@ with chemical compounds

  • In order to evaluate the influence of vesicle structure on the photostability of tretinoin, TRA-loaded vesicles were prepared by the film hydration method, extrusion technique and sonication [23].
  • After UV irradiation, TRA dissolved in methanol degraded very quickly while the incorporation in vesicles always led to a reduction of the photodegradation process [23].
  • However, the inclusion of TRA in P90H liposomes and Brij 30 or Triton CG110 niosomes retarded the drug photodegradation [23].
  • METHODS: We used polymerase chain reaction (PCR) for amplification of junctional region of rearranged IgH, TCRD and TCRG genes in combination with heteroduplex analysis in polyacrylamide gel [24].
  • By using in situ chromosomal hybridization and Southern blot analysis to examine RPMI 8402 cells, we determined that the break at 14q11 occurs within the variable region sequences of the T-cell receptor alpha-chain gene (TCRA); the break at 11p15 occurs between the HRAS1 gene and the genes for insulin and the insulin-like growth factor 2 [25].

Other interactions of TRA@


Analytical, diagnostic and therapeutic context of TRA@


  1. T cell receptor gamma (TCRG) gene rearrangements in T cell acute lymphoblastic leukemia refelct 'end-stage' recombinations: implications for minimal residual disease monitoring. Szczepański, T., Langerak, A.W., Willemse, M.J., Wolvers-Tettero, I.L., van Wering, E.R., van Dongen, J.J. Leukemia (2000) [Pubmed]
  2. Immunophenotypic and immunogenotypic characteristics of TCRgammadelta+ T cell acute lymphoblastic leukemia. Langerak, A.W., Wolvers-Tettero, I.L., van den Beemd, M.W., van Wering, E.R., Ludwig, W.D., Hählen, K., Necker, A., van Dongen, J.J. Leukemia (1999) [Pubmed]
  3. Cross-lineage T cell receptor gene rearrangements occur in more than ninety percent of childhood precursor-B acute lymphoblastic leukemias: alternative PCR targets for detection of minimal residual disease. Szczepański, T., Beishuizen, A., Pongers-Willemse, M.J., Hählen, K., Van Wering, E.R., Wijkhuijs, A.J., Tibbe, G.J., De Bruijn, M.A., Van Dongen, J.J. Leukemia (1999) [Pubmed]
  4. Molecular cytogenetic detection of chromosomal breakpoints in T-cell receptor gene loci. Gesk, S., Martín-Subero, J.I., Harder, L., Luhmann, B., Schlegelberger, B., Calasanz, M.J., Grote, W., Siebert, R. Leukemia (2003) [Pubmed]
  5. Disruption of the BCL11B gene through inv(14)(q11.2q32.31) results in the expression of BCL11B-TRDC fusion transcripts and is associated with the absence of wild-type BCL11B transcripts in T-ALL. Przybylski, G.K., Dik, W.A., Wanzeck, J., Grabarczyk, P., Majunke, S., Martin-Subero, J.I., Siebert, R., Dölken, G., Ludwig, W.D., Verhaaf, B., van Dongen, J.J., Schmidt, C.A., Langerak, A.W. Leukemia (2005) [Pubmed]
  6. A phase I trial of beta-all-trans-retinoic acid delivered via a collagen sponge and a cervical cap for mild or moderate intraepithelial cervical neoplasia. Meyskens, F.L., Graham, V., Chvapil, M., Dorr, R.T., Alberts, D.S., Surwit, E.A. J. Natl. Cancer Inst. (1983) [Pubmed]
  7. T-cell receptor variable genes and genetic susceptibility to celiac disease: an association and linkage study. Roschmann, E., Wienker, T.F., Gerok, W., Volk, B.A. Gastroenterology (1993) [Pubmed]
  8. Lysinuric protein intolerance (LPI) gene maps to the long arm of chromosome 14. Lauteala, T., Sistonen, P., Savontaus, M.L., Mykkänen, J., Simell, J., Lukkarinen, M., Simell, O., Aula, P. Am. J. Hum. Genet. (1997) [Pubmed]
  9. Phase II study of all-trans-retinoic acid and alpha-interferon in patients with advanced non-small cell lung cancer. Athanasiadis, I., Kies, M.S., Miller, M., Ganzenko, N., Joob, A., Marymont, M., Rademaker, A., Gradishar, W.J. Clin. Cancer Res. (1995) [Pubmed]
  10. Phase II trial of oral beta-all trans-retinoic acid in hepatocellular carcinoma (SWOG 9157). Meyskens, F.L., Jacobson, J., Nguyen, B., Weiss, G.R., Gandara, D.R., MacDonald, J.S. Investigational new drugs. (1998) [Pubmed]
  11. Amino acid uptake in isolated, perfused liver: effect of trauma and sepsis. Sax, H.C., Hasselgren, P.O., Talamini, M.A., Edwards, L.L., Fischer, J.E. J. Surg. Res. (1988) [Pubmed]
  12. Thyroid stimulating hormone receptor antibody in thyroid diseases. Vadivelu, N., Stephen, D.C., Kanagasabapathy, A.S., Seshadri, M.S. Indian J. Med. Res. (1990) [Pubmed]
  13. Human T-cell lines with well-defined T-cell receptor gene rearrangements as controls for the BIOMED-2 multiplex polymerase chain reaction tubes. Sandberg, Y., Verhaaf, B., van Gastel-Mol, E.J., Wolvers-Tettero, I.L., de Vos, J., Macleod, R.A., Noordzij, J.G., Dik, W.A., van Dongen, J.J., Langerak, A.W. Leukemia (2007) [Pubmed]
  14. T-cell prolymphocytic leukaemia: antigen receptor gene rearrangement and a novel mode of MTCP1 B1 activation. De Schouwer, P.J., Dyer, M.J., Brito-Babapulle, V.B., Matutes, E., Catovsky, D., Yuille, M.R. Br. J. Haematol. (2000) [Pubmed]
  15. Non-HLA genetic factors and insulin dependent diabetes mellitus in the Japanese: TCRA, TCRB and TCRG, INS, THY1, CD3D and ETS1. Aparicio, J.M., Wakisaka, A., Takada, A., Matsuura, N., Yoshiki, T. Dis. Markers (1990) [Pubmed]
  16. Immunoglobulin and T-cell receptor gene rearrangement and expression in human lymphoid leukemia cells at different stages of maturation. Davey, M.P., Bongiovanni, K.F., Kaulfersch, W., Quertermous, T., Seidman, J.G., Hershfield, M.S., Kurtzberg, J., Haynes, B.F., Davis, M.M., Waldmann, T.A. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  17. The incidence of clonal T-cell receptor rearrangements in B-cell precursor acute lymphoblastic leukemia varies with age and genotype. Brumpt, C., Delabesse, E., Beldjord, K., Davi, F., Cayuela, J.M., Millien, C., Villarese, P., Quartier, P., Buzyn, A., Valensi, F., Macintyre, E. Blood (2000) [Pubmed]
  18. Sequence diversity, natural selection and linkage disequilibrium in the human T cell receptor alpha/delta locus. Mackelprang, R., Livingston, R.J., Eberle, M.A., Carlson, C.S., Yi, Q., Akey, J.M., Nickerson, D.A. Hum. Genet. (2006) [Pubmed]
  19. Basic helix-loop-helix proteins E2A and HEB induce immature T-cell receptor rearrangements in nonlymphoid cells. Langerak, A.W., Wolvers-Tettero, I.L., van Gastel-Mol, E.J., Oud, M.E., van Dongen, J.J. Blood (2001) [Pubmed]
  20. Chimeric gamma-delta signal joints. Implications for the mechanism and regulation of T cell receptor gene rearrangement. Tycko, B., Coyle, H., Sklar, J. J. Immunol. (1991) [Pubmed]
  21. Primers and protocols for standardized detection of minimal residual disease in acute lymphoblastic leukemia using immunoglobulin and T cell receptor gene rearrangements and TAL1 deletions as PCR targets: report of the BIOMED-1 CONCERTED ACTION: investigation of minimal residual disease in acute leukemia. Pongers-Willemse, M.J., Seriu, T., Stolz, F., d'Aniello, E., Gameiro, P., Pisa, P., Gonzalez, M., Bartram, C.R., Panzer-Grümayer, E.R., Biondi, A., San Miguel, J.F., van Dongen, J.J. Leukemia (1999) [Pubmed]
  22. Heteroduplex PCR analysis of rearranged T cell receptor genes for clonality assessment in suspect T cell proliferations. Langerak, A.W., Szczepański, T., van der Burg, M., Wolvers-Tettero, I.L., van Dongen, J.J. Leukemia (1997) [Pubmed]
  23. Niosomes as carriers for tretinoin. II. Influence of vesicular incorporation on tretinoin photostability. Manconi, M., Valenti, D., Sinico, C., Lai, F., Loy, G., Fadda, A.M. International journal of pharmaceutics. (2003) [Pubmed]
  24. Rearrangements of IgH, TCRD and TCRG genes as clonality marker of childhood acute lymphoblastic leukemia. Meleshko, A.N., Lipay, N.V., Stasevich, I.V., Potapnev, M.P. Experimental oncology. (2005) [Pubmed]
  25. T-cell receptor alpha-chain gene is split in a human T-cell leukemia cell line with a t(11;14)(p15;q11). Le Beau, M.M., McKeithan, T.W., Shima, E.A., Goldman-Leikin, R.E., Chan, S.J., Bell, G.I., Rowley, J.D., Diaz, M.O. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  26. Cyclin D2 dysregulation by chromosomal translocations to TCR loci in T-cell acute lymphoblastic leukemias. Clappier, E., Cuccuini, W., Cayuela, J.M., Vecchione, D., Baruchel, A., Dombret, H., Sigaux, F., Soulier, J. Leukemia (2006) [Pubmed]
  27. Sequence analysis of the human alpha beta T-cell receptor CDR3 region. Moss, P.A., Bell, J.I. Immunogenetics (1995) [Pubmed]
  28. Crystal structure of p14TCL1, an oncogene product involved in T-cell prolymphocytic leukemia, reveals a novel beta-barrel topology. Hoh, F., Yang, Y.S., Guignard, L., Padilla, A., Stern, M.H., Lhoste, J.M., van Tilbeurgh, H. Structure (1998) [Pubmed]
  29. A linkage study across the T cell receptor A and T cell receptor B loci in families with rheumatoid arthritis. Hall, F.C., Brown, M.A., Weeks, D.E., Walsh, S., Nicod, A., Butcher, S., Andrews, L.J., Wordsworth, B.P. Arthritis Rheum. (1997) [Pubmed]
  30. HLA and T-cell receptor polymorphisms in Belgian multiple sclerosis patients: no evidence for disease association with the T-cell receptor. Vandevyver, C., Buyse, I., Philippaerts, L., Ghabanbasani, Z., Medaer, R., Carton, H., Cassiman, J.J., Raus, J. J. Neuroimmunol. (1994) [Pubmed]
  31. Comparative analysis of Ig and TCR gene rearrangements at diagnosis and at relapse of childhood precursor-B-ALL provides improved strategies for selection of stable PCR targets for monitoring of minimal residual disease. Szczepański, T., Willemse, M.J., Brinkhof, B., van Wering, E.R., van der Burg, M., van Dongen, J.J. Blood (2002) [Pubmed]
  32. Chromosomal in situ hybridization of a Hodgkin's disease-derived cell line (L540) using DNA probes for TCRA, TCRB, MET, and rRNA. Fonatsch, C., Gradl, G., Kolbus, U., Rieder, H., Tesch, H. Hum. Genet. (1990) [Pubmed]
  33. Comparative sequence analysis of the human T cell receptor TCRA and TCRB CDR3 regions. Moss, P.A., Bell, J.I. Hum. Immunol. (1996) [Pubmed]
  34. Detection of antigen receptor gene rearrangements in lymphoproliferative malignancies by fluorescent polymerase chain reaction. Kerlan-Candon, S., Soua, Z., Lefranc, M.P., Clot, J., Eliaou, J.F. Tissue Antigens (1998) [Pubmed]
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