Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Most of the diversity in T cell receptor subunits resides in the region that is the equivalent of the CDR3 of immunoglobulins. In order to learn more about the relative contributions of the various mechanisms that generate this diversity we have analyzed the sequences of alpha chain transcripts from BALB/c thymus. The J alpha repertoire of BALB/c mice was examined by comparison of new J alpha sequences and previously published sequences. Among the 41 J alpha genes examined, most of the diversity is located at the 5' end, consistent with the notion that this region contacts the antigen. VJ junctional diversity was examined by sequencing various V alpha J alpha combinations derived from different stages of development. Deletion of bases from the ends of V and J genes does not occur with equal frequency. A greater number of bases were deleted on average from the ends of J genes. Bases were added at junctions frequently in isolates from adult animals, consistent with the presence of terminal deoxynucleotidyl transferase. However, there were short stretches of sequences at junctions which were also present at the 5' end of J genes. These findings extend recent observations that alpha chain genes use multiple mechanisms for generating diversity.
Mol Immunol 1992 Dec
PMID:Sequence diversity of T cell receptor alpha chain transcripts from BALB/c thymus. 128 Jul 58

In SPL2-1-2, a murine B-committed immature cell line transformed with a temperature-sensitive mutant of Abelson virus, T cell receptor (TCR) gamma gene rearrangements, together with IgH gene rearrangements, were induced during culture at a non-permissive temperature (39 degrees C). During 11-12 months of culture, TCR gamma gene rearrangements occurred in all cells. In contrast to TCR gamma genes, neither TCR beta or TCR delta were detected even after 11-12 months of culture at a non-permissive temperature. The majority of the TCR gamma gene rearrangements observed here were V gamma 2 to J gamma 2 joinings and the remaining rearrangements were J gamma 1-linked. V gamma 1 to J gamma 4 and V gamma 3 to J gamma 3 joinings were not detected. Approximately 70% of cells with TCR gamma gene rearrangements produced normal-sized transcripts from the rearranged TCR gamma genes. Cloning and sequencing analysis of a cDNA from the transcripts demonstrated that the whole structure of the cDNA was similar to that of T-lineage cells. These results showed that TCR gene rearrangements were restricted to the gamma genes and that V gamma 2 to J gamma 2 joinings occurred preferentially in this B-committed immature cell line. Furthermore, TCR gamma gene rearrangements also occurred in intracytoplasmic mu-chain producing cells. This indicated that the existence of intracytoplasmic mu-chains did not prevent TCR gamma gene rearrangements, although the existence of mu-chains is known to inhibit further productive IgH gene rearrangements, (allelic exclusion). These results should provide many implications for the mechanism of TCR gene rearrangements, especially that of cross-lineage rearrangements.
Mol Immunol 1992 Mar
PMID:Continuing V gamma 2 to J gamma 2 rearrangements of murine T cell receptor gamma genes in a B-committed immature cell line. 137 58

The immunosuppressive drugs FK506 and cyclosporin A have an identical spectrum of activities with respect to IgE receptor (Fc epsilon RI)-mediated exocytosis from mast cells and T cell receptor-mediated transcription of IL-2. These findings suggest a common step in receptor-mediated signal transduction leading to exocytosis and transcription and imply that immunosuppressive drugs target specific signal transduction pathways, rather than specific cell types. This hypothesis is supported by studies on the effect of rapamycin on IL-3 dependent proliferation of the rodent mast cell line PT18. Rapamycin inhibits proliferation of PT18 cells, achieving a plateau of 80% inhibition at 1 nM. This inhibition is prevented in a competitive manner by FK506, a structural analogue of rapamycin. Proliferation of rat basophilic leukemia cells and WEHI-3 cells was also inhibited, at doses comparable to those shown previously to inhibit IL-2-dependent proliferation of cytotoxic T lymphocyte line (CTLL) cells. In contrast, proliferation of A-431 cells, a epidermoid cell line, was not affected by rapamycin. DNA histograms indicate that complexes formed between the rapamycin-FK506-binding protein (FKBP) and rapamycin arrest-proliferating PT18 cells in the G0/G1-phase. It is concluded that FKBP-rapamycin complexes may inhibit proliferative signals emanating from IL-3 receptors, resulting in growth arrest of cytokine-dependent, hematopoietic cells.
Mol Biol Cell 1992 Sep
PMID:The effect of the immunophilin ligands rapamycin and FK506 on proliferation of mast cells and other hematopoietic cell lines. 138 15

We have used the anchored polymerase chain reaction (A-PCR) to clone and compare the 5' upstream regions of the human T cell receptor gamma (TRG) genes. Whereas little homology was found among subgroups I, II, III and IV, sequence alignment of TRG subgroup I members revealed a high degree of homology in the 5' sequences. A conserved heptamer sequence (CTGCAGG), which was found upstream from the translation initiation site of all TRG genes in our analysis. Determination of the transcription initiation site located the conserved heptamer 65 base pairs upstream from the cap sites of V5. No TATA box or other cis-acting promoter sequences could be identified in any of the human TRG upstream sequences.
Mol Immunol 1992 Sep
PMID:The human T cell receptor gamma genes are transcribed from TATA-less promoters containing a conserved heptamer sequence. 138 51

In human peripheral blood, most of the CD3+ cells express the alpha/beta T cell receptor. A smaller fraction of CD3+ T cells express the gamma/delta T cell receptor (from 1 to 10% depending the individuals, with an average of 3-5%). Interestingly, although the alpha/beta + T cells never express the gamma chain at the cell surface, most of them (about 98%) rearrange the gamma locus on both alleles, the remaining 2% alpha/beta + T cells have one rearranged TRG locus. We previously proposed that V-J joinings in the human TRG locus occurred sequentially and we recently demonstrated that two successive rearrangements may occur on the same chromosome [Alexandre et al. (Int. Immunol, 3, 973-982, 1991)]. In this paper, we discuss the implications of these sequential rearrangements on the relatedness of the human gamma/delta + and alpha/beta + T cell lineages.
Mol Immunol 1992 Apr
PMID:The human gamma/delta + and alpha/beta + T cells: a branched pathway of differentiation. 153 10

This study describes the secretion and purification of T cell receptor (TCR) V alpha, V beta domains and single chain V alpha-V beta fragments (scTCRs) from recombinant Escherichia coli cells. The TCR V alpha and V beta genes are derived from a T cell hybridoma that is associated with disease pathogenesis in murine experimental allergic encephalomyelitis (EAE). Circular dichroism (c.d.) analyses of the single domains and the scTCR indicate that they are folded into beta-pleated sheet structures similar to those of immunoglobulin variable domains. The secreted TCR fragments can be purified in milligram quantities, and could therefore be used in high-resolution structural studies, in immunization to generate anti-clonotypic antibodies or in vaccination.
J Mol Biol 1992 Apr 20
PMID:Secretion of T cell receptor fragments from recombinant Escherichia coli cells. 153 51

The immunosuppressive drug mizoribine has been demonstrated to inhibit T lymphocyte proliferation by depleting these cells of guanine ribonucleotides as a consequence of inhibiting the enzyme inosine monophosphate (IMP) dehydrogenase. Because the immunosuppressive agents azathioprine and 6-mercaptopurine (6MP) are both converted to the IMP analog 6-thio-IMP, we postulated that these drugs might inhibit T cell activation and/or proliferation by a similar mechanism. Incubation of isolated peripheral blood T cells with either mizoribine or the selective IMP dehydrogenase inhibitor mycophenolic acid caused a dose-dependent inhibition of T cell proliferation, which was reversible with the addition of 50 microM guanosine to replete guanine ribonucleotide pools. In contrast, guanosine exacerbated the inhibition of proliferation induced by azathioprine and restored proliferation at IC50 concentrations of 6MP by only 10%. Complete restoration of proliferation in the presence of 6MP, but not azathioprine, was achieved with the addition of adenine. The inhibitory effects of azathioprine, as well as those of mizoribine, 6MP, and mycophenolic acid, were identical in cells stimulated with antibody to the T cell receptor and in cells stimulated with phorbol ester and ionomycin. We conclude from these studies that mizoribine selectively inhibits guanine ribonucleotide formation in purified T cells, whereas the effect of 6MP appears to be more dependent on adenine ribonucleotide depletion. Azathioprine, on the other hand, inhibits proliferation by a mechanism independent of purine ribonucleotide depletion. None of these agents inhibits T cell proliferation by interfering with signal transduction mediated by the T cell receptor. Inhibition of guanine ribonucleotide biosynthesis appears to be a novel and perhaps more selective mechanism of inhibiting T cell proliferative responses after T cell activation.
Mol Pharmacol 1992 Apr
PMID:Comparison of the effects of mizoribine with those of azathioprine, 6-mercaptopurine, and mycophenolic acid on T lymphocyte proliferation and purine ribonucleotide metabolism. 156 21

Beef insulin-specific I-Ad-restricted T cell hybridomas were derived from the fusion of antigen-primed (BALB/c X B6)F1 T cells with BW5147 thymoma. Specificity analysis revealed that the A-chain loop region is involved in antigen recognition. Hybridoma A20.2.15 is specific for beef insulin and cross-reacted with sheep insulin, but not with pork insulin. Using synthetic peptides we showed that the A-chain loop containing peptide A1-A14 jointed to the B7-B15 peptide by a disulfide bond can activate this hybridoma. Fragments generated by enzyme digest further suggest that the peptide recognized on beef insulin appears to involve A-chain loop residues A5-A12 and B-chain residues B7-B13 that are linked by the A7-B7 disulfide bridge. We found that beef insulin needs to be processed prior to T cell activation. Glutaraldehyde fixation and chloroquine treatment of presenting cells abolished their capacity to present insulin. Beef insulin denatured by pH changes cannot activate, thus suggesting that simple denaturation is not sufficient for presentation by antigen presenting cells. Finally, the agretope on beef insulin is comprised of two functional regions B7-B13 on the B chain and the A-chain loop in the A-chain, while residues A8 and A10 are probably involved in interaction with the T cell receptor.
Mol Immunol 1990 Jul
PMID:Characterization of agretopes and epitopes involved in the presentation of beef insulin to T cells. 169 43

The requirements for insulin presentation and recognition by A alpha b A beta b- and A alpha b A beta k-restricted mouse T cells were studied using a variety of derivatives of the insulin A chain. It was found that A chain peptides with irreversibly blocked Cys residues are non-stimulatory for the T cells. This suggests that at least one of the Cys residues is essential for recognition. On the other hand, all A chain peptides containing Cys residues modified in a way reversible by reaction with thiols are stimulatory yet differ in antigenic potency. All these A chain derivatives including a 14 amino acid fragment require uptake by antigen presenting cells (APC) for efficient presentation. Differences in stimulatory potency between the A chain peptides derived from the same insulin appear to be mainly due to the efficiency of uptake and/or processing by APC. Based on these findings we propose that processing in the case of insulin and its A chain derivatives involves the reductive deblocking of Cys residues or the rearrangement of disulfide bonds apart from a possible proteolytic cleavage. The same may apply to other proteins if Cys residues in the presented peptides are important for the interaction with Ia or the T cell receptor.
Mol Immunol
PMID:Presentation of insulin and insulin A chain peptides to mouse T cells: involvement of cysteine residues. 171 73

Glycosphingolipids added to the cell culture medium can be incorporated into the plasma membrane and interfere with the growth of certain cell types. In the past years, previous reports have shown that gangliosides, a class of glycosphingolipids bearing sialic acid can inhibit antigen or mitogen induced T cell proliferative responses in vitro. We report here that the inhibition of PHA induced proliferation by the trisialoganglioside GT1b was not reversed by addition of exogenous IL-1, IL-2, TPA and calcium ionophore. Furthermore, GT1b did not affect IL-2 production by activated T cells. In addition, GT1b ganglioside could also decrease strongly the expression of the T cell antigens CD3, CD2, CD4, CD8 and the alpha/beta T cell receptor antigenic complex whereas it did not affect HLA-class I antigens. By contrast, GT1b modulated only partially membrane expression of activation antigens such as CD25 (Tac) and transferrin receptor and increased the expression of HLA-class II antigens. Moreover CD25 messenger RNA induction was not affected by GT1b treatment of PHA-stimulated T cells. Our results demonstrate that gangliosides, in spite of their anti-proliferative capacity and their modulation effect on T cell antigen membrane expression, do not prevent the progression of T cells into early stages of the activation process.
Mol Immunol 1991 Nov
PMID:Analysis of phenotypic and functional changes during ganglioside-induced inhibition of human T cell proliferation. 183 57


1 2 3 4 5 6 7 8 9 10 Next >>