Disease relevance of Genes, T-Cell Receptor

• OBJECTIVE--To evaluate the role of candidate genes in the susceptibility to multiple sclerosis (MS) and describe the role of T-cell receptor (TCR) gene rearrangements in the MS brain lesion in identifying a major target of the immune response in this disease [1].
• A variety of rearranged variable TCR genes was found in polymyositis, V alpha 1, V alpha 5, V beta 1, and V beta 15 being the most common (present in 60-100% of patients) [2].
• Despite resolution of neutropenia, increased populations of T-LGL cells have persisted in all patients during CSA therapy, as shown by morphology and flow cytometry and by the presence of clonal TCR gene rearrangements in four patients' posttreatment blood samples [3].
• We investigated the arrangement of Ig and T-cell receptor (TCR) genes, together with the involvement of several oncogenes and the tumor-suppressor gene p53, in a panel of primary cutaneous B- and T-cell lymphomas (CBCLs and CTCLs) [4].
• Finally, karyotype and chromosome painting analyses showed no evidence for TCR gene translocations in p53-deficient thymomas, although abundant aneuploidy involving frequent duplication of certain chromosomes was present [5].

High impact information on Genes, T-Cell Receptor

• T cell receptor (TCR) transgenic mice have been made from the rearranged TCR genes of several of these, of which that specific for H-Y/Db is the best studied [6].
• Both HLA and TCR genes have been linked to susceptibility for MS which is widely believed to be mediated by T cells that recognize an as yet unidentified autoantigen [7].
• The results support the theory that RAG1 and RAG2 were once components of a transposable element, and that the split nature of immunoglobulin and T-cell-receptor genes derives from germline insertion of this element into an ancestral receptor gene soon after the evolutionary divergence of jawed and jawless vertebrates [8].
• Here we track the outcome of in vivo interactions between B cells and CD4+ T cells that recognize a transgene-encoded autoantigen, hen egg lysozyme (HEL), using cells from mice transgenic for immunoglobulin and T-cell receptor (TCR) genes [9].
• These findings suggest that D delta 1, D delta 2, and J delta 1 may be among the first TCR gene elements to undergo recombination and that scid T-lineage cells are developmentally arrested during or shortly after this stage of differentiation [10].

Chemical compound and disease context of Genes, T-Cell Receptor

• The present study of the polymerase chain reaction (PCR) as a diagnostic tool in early mycosis fungoides was therefore undertaken, using a rapid PCR method for the detection of gamma- and beta-chain T-cell receptor (TCR) gene rearrangements in routine formalin-fixed, paraffin-embedded histological sections [11].
• To determine whether the *Tcr gene product modified tetracycline, we characterized the material resulting from incubation of E. coli (*Tcr) with tetracycline [12].
• Recently it has been reported that the intrathyroidal T cells in Graves' disease display restriction in V alpha T cell receptor (TcR) gene family usage, although this is not found with TcR V beta gene families in the same individuals [13].

Biological context of Genes, T-Cell Receptor

• Interestingly, there is a coincident selective and transient down-regulation of the protein RAG2, on which TCR gene rearrangement obligatorily depends [14].
• The TCR gene was placed under the control of the human beta-actin promoter and enhancer [15].
• Apparently, the N-terminal truncated RAG1 protein can recombine TCR genes but not immunoglobulin genes [16].
• RS recombinations appear to be mediated by the same mechanisms involved in Ig and TCR gene rearrangement [17].
• CONCLUSION: Our data suggest that a TCR gene segment in or linked to this 47-kb region may be involved in genetic susceptibility to RA through an interaction with HLA-DR4 [18].

Anatomical context of Genes, T-Cell Receptor

• Induction of TCR gene rearrangements in uncommitted stem cells by a subset of IL-7 producing, MHC class-II-expressing thymic stromal cells [19].
• However, as shown here, germ-line transcripts of B cell immunoglobulin (Ig) constant and variable region genes and of T cell receptor (TCR) genes are detectable in lymphopoietic tissues of scid mice, as well as B and T lineage-specific lambda 5 and T3 delta transcripts [20].
• The tissue- and stage-specific assembly of Ig and TCR genes is mediated by a common V(D)J recombinase complex in precursor lymphocytes [21].
• Bulk populations and 39 hybridomas from splenic Con A cultures were analyzed for rearrangements among TCR genes: alpha, beta, gamma, and delta [22].
• Extrathymic TCR gene rearrangement in human small intestine: identification of new splice forms of recombination activating gene-1 mRNA with selective tissue expression [23].

Associations of Genes, T-Cell Receptor with chemical compounds

• In the present study, a longitudinal analysis of T cell receptor (TCR) gene usage by CTL clones was performed in a seropositive person using TCR gene sequences as a means of tracking responses to a well-defined epitope in the glycoprotein 41 transmembrane protein [24].
• Here we report that the lymphocyte-specific protein tyrosine kinase p56lck, when overexpressed in developing thymocytes, provokes a reduction in V beta--D beta rearrangement while permitting normal juxtaposition of other TCR gene segments [25].
• These findings underscore the role of gut CP in the early extrathymic maturation of CD8alphaalpha+ IEL, including cell-surface expression of alphaEbeta7 integrin, CD3epsilon gene transcription, and TCR gene rearrangements [26].
• Also, TCR-defective Jurkat T cells transfected with gammadelta TCR genes produced a significant level of IL-2 in response to the pamidronate-pulsed THP-1 cells [27].
• The TRGV-J and TRDV-D-J rearrangements expressed by IPP-stimulated Aotus and human gammadelta T cells were similar with respect to 1) TCR gene segment usage, 2) a high degree of germline sequence homology of the TCR gene segments used, and 3) the diversity of the CDR3 regions [28].

Gene context of Genes, T-Cell Receptor

• Moreover, during the IL-2-mediated maturation process rearrangements and expression of both alpha and beta chain TCR genes occurred, and resulted in the acquisition of alpha/beta as well as gamma/delta (either disulphide-linked or non-disulphide-linked) heterodimeric TCR among the pro-T cell progeny [29].
• We have isolated a full-length human Gata3 cDNA and characterized its role in TCR gene regulation [30].
• Investigated was whether cotransfection of RAG1 and RAG2 genes in combination with lymphoid transcription factors can induce TCR gene rearrangements in nonlymphoid human cells [31].
• We show that mouse Dad1 has a broader expression pattern than the TCR genes, in terms of both tissue and temporal specificity [32].
• Perhaps as a result of reduced proliferation, the accumulation of RAG-2 protein in the DN thymocytes is increased in B7-deficient mice, which may explain the increased expression of TCR gene and accelerated transition of CD25(+)CD44(-) (DN3) to CD25(-)CD44(-) (DN4) stage [33].

Analytical, diagnostic and therapeutic context of Genes, T-Cell Receptor

• Relapse blast cells were shown to express the common ALL antigen (CD 10) in all cases and an identical clonal IgH or TCR gene rearrangement was found on PCR analysis of DNA from diagnosis and relapse in all eight cases where DNA extraction was successful [34].
• V beta 2 TCR expression from these patients was analyzed more extensively using a combination of individual TCR gene cloning, followed by sequence analysis [35].
• By using Southern blot analysis, the described rearranged TCR genes can be detected in the J alpha junctional region and in the J beta 2 cluster on the genomic DNA level [36].
• The finding that two gp100-specific TCR, derived from two different CTL, can be functionally introduced into primary human T lymphocytes without loss of the Ag reactivity and peptide fine specificity, holds great promise for the application of TCR gene transfer in cancer immunotherapy [37].
• Case-specific clonal rearrangements of IgH and TCR genes and expression levels of Wilms' tumor 1 (WT1) mRNA were determined by PCR or RT-PCR methods [38].

References