Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.48 (transcriptase)
9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The murine B7-1 (mB7-1) molecule expressed on APCs delivers a costimulatory signal for T cell activation through its T cell counter-receptor CD28, resulting in T cell proliferation and IL-2 production. Signaling through the TCR in the absence of CD28 signaling results in T cell anergy. We have analyzed the genomic structure of mB7-1 and here describe the identification of a previously unrecognized sixth exon at the far 3' end of the locus, which encodes an alternative cytoplasmic domain. Reverse transcriptase-PCR amplification of mB7-1 transcripts demonstrates that exon 6 is functionally spliced to the transmembrane-encoding exon 4. Furthermore, using 5' rapid amplification of cDNA ends, we determined that the 5'-untranslated region extends over 1505 bp beyond the previously reported transcriptional start site. In addition, we report the chromosomal location of mB7-1 to chromosome 16, band B5.
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PMID:Characterization of the murine B7-1 genomic locus reveals an additional exon encoding an alternative cytoplasmic domain and a chromosomal location of chromosome 16, band B5. 752 22

The idiopathic inflammatory myopathies (IIM) are a heterogeneous group of diseases in which autoreactive T cells are thought to play a pathogenetic role. We have determined the pattern of TCR-alpha beta gene expression by muscle-infiltrating lymphocytes within clinically and serologically defined groups of IIM patients. We utilized the PCR to study TCR V gene expression in muscle biopsies from nine polymyositis (PM) and eight dermatomyositis (DM) patients, all of whom had autoantibodies directed against histidyl-transfer RNA synthetase (anti-Jo-1 autoantibodies). While the TCR repertoire in DM patients was generally polyclonal, an oligoclonal profile characterized PM patients. Certain V gene families were predominantly expressed; V alpha 1 and V beta 6 gene families were detected in 82 and 91% of PM biopsies, respectively. TCR expression was characterized further by analyzing J gene usage from four PM patients expressing the V beta 6 gene. Sequence analysis of 40 independent recombinants (10 per patient) identified only seven V beta 6 clonotypes and restricted usage of the related J beta 2.1, -2.3, and -2.7 genes. These data, describing predominant TCR V and J gene usage by muscle-infiltrating lymphocytes in myositis patients, suggest that Ag-driven T cell responses may play a primary role in mediating some forms of the IIM.
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PMID:Predominant TCR-alpha beta variable and joining gene expression by muscle-infiltrating lymphocytes in the idiopathic inflammatory myopathies. 813 64

Alloreactivity against micromismatches in MHC class I molecules is difficult to measure. Here, we describe an in vitro model with which it is possible to examine alloreactivity against a single HLA class I allotype. The HLA class I- and class II-negative myelocytic leukemia cell line K562 was transfected with a genomic DNA clone carrying B*4403 to express a single allotype. CTL lines were generated from normal individuals carrying B*4402, B*4403, or unrelated HLA-B alleles by stimulation with B*4403- transfected K562. The bulk CTL lines generated from B*4402+ T cells against B*4403 that carry a single amino acid disparity at position 156 were specific for B*4403+ targets and did not react with targets carrying any other HLA allotype. However, the CTL lines generated from B44-negative individuals exhibited killing of the targets bearing not only B44, but also B44 CREG and a few other B alleles. Reverse transcriptase-PCR analysis of TCRs, expressed in the CTL clones uniquely specific for B*4403, showed that TCR V beta usage of alloreactive T cells directed against B*4403 was diverse but nonrandom and was affected by the HLA background of the responder. Thus, the K562-HLA transfectant system provides a useful in vitro tool to analyze alloreactivity against a single class I allele and to aid in the prediction of alloreactivity in unrelated marrow transplantation.
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PMID:Induction of microvariant-specific CTL lines reactive to a single amino acid mismatch in bulk cultures using a transfectant expressing a single HLA class I molecule. 859 60

Oral squamous cell carcinoma (OSCC) are frequently infiltrated by tumour infiltrating lymphocytes (TILs) which may demonstrate specific anti-tumour cytotoxicity. We have used a panel of family-specific primers in reverse-transcriptase (RT)-polymerase chain reactions (PCR) to determine the TCR Vbeta repertoire of TILs in the primary and metastatic tumours in patients with OSCC. We observed a diverse and heterogenous usage of TCR Vbeta genes by TILs in the primary tumours, a scenario not unlike normal oral mucosal lymphocytes. In one patient with a longstanding history of OSCC, the repertoire was restricted. Restricted TCR Vbeta gene usage also occurred in TILs of metastatic tumours. Within individual patients, discrepancies of TCR Vbeta gene usage were also observed between TILs in the primary OSCC and those in metastatic lymph nodes. Work is ongoing to determine the clonality and functional significance of these TILs.
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PMID:T cell receptor Vbeta repertoire of tumour-infiltrating lymphocytes in oral squamous-cell carcinoma. 862 69

We report that I-Ab-restricted T cell clones, elicited by influenza infection of C57BL/10 mice and specific for the hemagglutinin peptide HA1 186-205, express class II. They respond to peptide stimulation by IL release (IL-3 or IFN-gamma) without a requirement for APC but do not proliferate. Moreover, surface expression of class II requires de novo synthesis in the presence of the stimulatory peptide and is inhibited by coculture with TCR-specific Ab, or brefeldin A or cycloheximide. Clonotypic specificity of peptide induction was confirmed by failure of other allele specific peptides to enhance class II expression. Addition of the viral peptide to T cells induced homotypic adhesion, which provides a physical basis for stabilization of class II-peptide complexes at the cell surface. Extinction of class II expression was evident in the corresponding T cell hybridomas, which might account for the failure to report class II expression by murine T cells. Control studies indicated that class II was not passively acquired from APC by demonstrating 1) failure of processed Ag to induce class II expression, 2) allo-class II (Ak) was not acquired by coculture with peptide and semisyngeneic (H-2 b/k) APC, 3) absence of class II expression by a NP peptide-specific Th2 clone under identical culture conditions, and most significantly, 4) reverse-transcriptase PCR amplification and surface expression of class II using highly purified preparations of FACS-selected CD4+ class II- cells cocultured with the stimulatory peptide.
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PMID:Viral peptide specific induction of MHC class II expression by murine T cell clones. 880 37

Granulocyte-macrophage colony-stimulating factor, mobilized peripheral blood stem cell (PSC) products, and peripheral blood leukocytes posttransplantation contain cells that cause allogeneic and autologous T cell apoptosis. Isolation and characterization of these cells demonstrated that they were low-density (Percoll fractionation) CD14+ monocytes. T cells in PSC products have a depressed phytohemagglutinin (PHA) mitogenic response; however, purified CD4+ or CD8+ T cells exhibit a statistically normal mitogenic function. Furthermore, no T cell inhibitory activity was observed in CD14+, CD4+, and CD8+ cell-depleted fractions enriched in CD4- CD8- TCR alpha/beta+ T cells. Inhibition of T cell function by CD14+ monocytes required cell-cell contact, and the analyses of DNA fragmentation by Southern and TUNEL analysis demonstrates an activation-induced T cell apoptosis in the presence of CD14+ monocytes. Reverse-transcriptase polymerase chain reaction studies suggested that high levels of interleukin-10 or tumor necrosis factor gene transcripts in the PSC products may contribute to the inhibition of T cell function.
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PMID:Monocytes from mobilized stem cells inhibit T cell function. 912 7

To explore the possible role of purinergic receptors in thymocyte development and in pathogenesis of adenosine deaminase SCID, we studied effects of extracellular adenosine triphosphate (ATP(ext)) and adenosine on TCR- and steroid hormone-triggered processes in mouse thymocytes. Reverse transcriptase-PCR analysis confirms the mRNA expression of several types of purinergic receptors, while the functioning of ATP receptors in thymocytes is reflected by ATP(ext)-induced intracellular calcium increases and by thymocyte subset-specific sensitivity to the effects of ATP(ext) and adenosine. Only ATP(ext), but not the ATP catabolites, adenosine, dexamethasone, or TCR cross-linking, was efficient in triggering rapid protein synthesis independent lysis of CD4+8- thymocytes and peripheral CD4+ T cells. In contrast, extracellular adenosine specifically induced the apoptosis of CD4+8+ thymocytes. ATP(ext) also induced a slower process of DNA fragmentation and protein synthesis-dependent apoptosis in all thymocyte subsets. ATP(ext) had an additive effect with TCR cross-linking in the induction of thymocyte death, but, unexpectedly, the effects of ATP(ext) at high concentration were antagonistic to steroid-induced apoptosis. Described here, the properties of ATP(ext) and adenosine are consistent with their involvement in the regulation of T cell development due to differential expression and signaling through purinergic receptors in different thymocyte subsets. The possible role of purinergic receptor signaling in T cell differentiation and adenosine deaminase SCID is discussed.
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PMID:Effects of extracellular ATP and adenosine on different thymocyte subsets: possible role of ATP-gated channels and G protein-coupled purinergic receptor. 916 24

Substance P (SP) is an immunoregulatory tachykinin which augments antigen- and mitogen-induced lymphocyte proliferation via signaling through the neurokinin-1 receptor (NK1-R). Non-neuronal cells of the immune system such as monocytes, T lymphocytes and eosinophils can be a source of SP. We have investigated if antigen-presenting dendritic cells (DC) produce SP. DC were grown from bone marrow precursors using a cocktail of GM-CSF, IL-4 and Flt-3 ligand. Reverse transcriptase-PCR amplification using primers for the mouse preprotachykinin-A gene and direct DNA sequencing of amplified products from purified DC demonstrated the presence of the gamma-transcript of the gene, coding for SP and neurokinin A. At the protein level, mouse DC expressed SP as determined by an enzyme immunoassay and confirmed by immunostaining. The functional role of endogenous SP release was determined. During the interaction with syngeneic or allogeneic DC, the addition of a specific NK1-R antagonist partly reduced proliferation in responding T lymphocytes. This was confirmed by using responders derived from NK1-R-deficient mice. In the absence of DC, proliferation of T cells induced by direct TCR ligation and soluble CD28 was partly dependent on signaling through NK1-R, revealing an autocrine effect of SP production by T cells. In conclusion, these results demonstrate that endogenously produced SP contributes to T cell proliferation induced by DC or TCR / CD28 stimulation.
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PMID:Endogenously produced substance P contributes to lymphocyte proliferation induced by dendritic cells and direct TCR ligation. 1060 89

Interleukin-7 (IL-7) has been shown to play an essential role in T-cell development. Recombinase-activating gene (RAG)-1, RAG-2 and pre-TCR-alpha expression in the normal adult human liver (AHL), together with the presence of lymphoid-haematopoietic progenitors, is strong evidence that the AHL supports T cell maturation. We investigated IL-7 mRNA and protein levels in order to determine whether AHL could support T lymphocyte differentiation. Biopsies were snap frozen, powdered, and RNA/protein extracted. Reverse transcriptase polymerase chain reaction was used to detect IL-7 using primers that amplified 620 base pair (bp) fragments and other smaller transcripts. A sandwich enzyme-linked immunosorbent assay was developed to quantify IL-7 protein in homogenates. The anatomic distribution of IL-7-secreting cells was determined by immunohistochemistry. IL-7-specific product (620 bp) was detected in nine of ten samples, with six also positive for a smaller splice-variant (488 bp). Levels of the 620 bp product were 2.5 times greater than the 488 bp fragment. IL-7 protein was detected in all samples (range 18.47-76.93 pg/100 mg tissue). Immunohistochemistry demonstrated IL-7 protein in discrete cells of lymphoid morphology, widely distributed throughout the parenchyma and within portal tracts. Large populations of innate T cells are found in normal AHL, some of which may differentiate locally. The presence of IL-7 RNA and protein throughout normal hepatic tissue provides evidence that the normal AHL is a suitable microenvironment for T cell differentiation.
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PMID:Expression of interleukin 7 (IL-7) mRNA and protein in the normal adult human liver: implications for extrathymic T cell development. 1139 92

This report describes an unusual extramedullary hematologic malignancy in an 18-month-old child who presented with a capillary leak syndrome that evolved into hyperleukocytosis with malignant cells. The circulating tumor cells did not express an antigen profile typical of any subtype of leukemia commonly observed in children. Tumor cells were CD3(-)/CD56(+); had germline TCR genes; and strongly expressed CD30, epithelial membrane antigen, and anaplastic lymphoma kinase (ALK) consistent with a null cell anaplastic large cell lymphoma (ALCL). The malignant cells contained a t(2;19)(p23;p13.1) that interrupted ALK and translocated it to the der(19). Reverse transcriptase-polymerase chain reaction and nucleotide sequence analysis revealed fusion of ALK to tropomyosin 4, an ALK fusion partner not described previously in hematologic malignancies. The clinical presentation and phenotypic features of this malignancy were not typical for ALCL because tumor cells expressed both myeloid (CD13, CD33, HLA-DR) and natural killer (NK) cell antigens. The neoplastic cells most resembled NK cells because in addition to being CD3(-)/CD56(+) with germline TCR genes, these cells were CD25(+)/CD122(+)/granzyme B(+) and possessed the functional properties of immature NK cells. The unusual clinical presentation, immunophenotype, and functional properties of these neoplastic cells suggest that this malignancy may be derived from the putative myeloid-NK precursor cell. Furthermore co-expression of NK and ALCL features supports the concept that a minority of null-ALCL may be derived from NK cells and expands the spectrum of phenotypes that can be seen in tumors produced by ALK fusion proteins. (Blood. 2001;98:1209-1216)
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PMID:Unusual childhood extramedullary hematologic malignancy with natural killer cell properties that contains tropomyosin 4--anaplastic lymphoma kinase gene fusion. 1149 72


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