Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A selective CD3 gamma defect, involving point mutations in both the paternal and the maternal genes, has been analyzed. The CD3 gamma defect affected two brothers of a four sibs family; one of them died at the age of 3 of a viral pneumonia with concomitant autoimmune features (Haemolytic anaemia and gut epithelial cell autoantibodies), whereas the other is still alive at the age of 10 with relatively mild infection episodes. In this work, the effects of the absence of the CD3 gamma chain in the structure and signal transduction of the T-cell receptor (TCR)/CD3 complex and in the selection and function of T lymphocytes were studied. The absence of CD3 gamma did not prevent the expression of certain amounts of TCR/CD3 complexes on the surface of T lymphocytes. This suggests the existence of at least two TCR/CD3 isoforms in T cells, either with or without CD3 gamma. A persistent low proportion of CD8+ T cells, not functional in vitro (they were unable to proliferate) and probably in vivo (associated to a lethal viral pneumonia), was observed. In contrast, the proportion of CD4+ T cells was not altered, and they were functional both in vitro (they showed a normal proliferation and a low, but detectable, increase of cytosolic Ca2+ in response to anti-TCR/CD3 stimuli, although the production of IL-2 was impaired) and in vitro (they normally helped B cells). These results show that the absence of CD3 gamma affects the selection and function of cytotoxic, but apparently not helper, T lymphocytes, although the possibility that the CD4+ T cells represent a specific subpopulation can not be ruled out. They also suggest that the interactions of the TCR/CD3 complex with its co-receptors during thymic selection and antigen recognition in the periphery may be asymmetrical, with CD8 interacting through CD3 gamma and, probably, CD4 through the homologous CD3 delta.
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PMID:T lymphocyte signalling defects and immunodeficiency due to the lack of CD3 gamma. 790 75

Arginine methylation is a post-translational modification resulting in the generation of aDMAs (asymmetrical omega-NG, NG-dimethylated arginines) and sDMAs (symmetrical omega-NG, N'G-dimethylated arginines). The role of arginine methylation in cell signalling and gene expression in T lymphocytes is not understood. In the present study, we report a role for protein arginine methylation in regulating IL-2 (interleukin 2) gene expression in T lymphocytes. Leukaemic Jurkat T-cells treated with a known methylase inhibitor, 5'-methylthioadenosine, had decreased cytokine gene expression, as measured using an NF-AT (nuclear factor of activated T-cells)-responsive promoter linked to the luciferase reporter gene. Since methylase inhibitors block all methylation events, we performed RNA interference with small interfering RNAs against the major PRMT (protein arginine methyltransferases) that generates sDMA (PRMT5). The dose-dependent decrease in PRMT5 expression resulted in the inhibition of both IL-2- and NF-AT-driven promoter activities and IL-2 secretion. By using an sDMA-specific antibody, we observed that sDMA-containing proteins are directly associated with the IL-2 promoter after T-cell activation. Since changes in protein arginine methylation were not observed after T-cell activation in Jurkat and human peripheral blood lymphocytes, our results demonstrate that it is the recruitment of methylarginine-specific protein(s) to cytokine promoter regions that regulates their gene expression.
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PMID:Arginine methylation regulates IL-2 gene expression: a role for protein arginine methyltransferase 5 (PRMT5). 1565 70

The biological purpose of the mature, postthymic CD8(+) T cell is to respond to microbial antigens with a developmental program of clonal expansion and concomitant differentiation leading to effector cells (T(EFF)) that provide antimicrobial defense. Because many microbial infections persist into a chronic phase, this antigen-stimulated developmental program must be capable of continually generating T(EFF), perhaps for the lifetime of the individual. This chapter proposes that the ability of a CD8(+) T cell clone to maintain the continual production of T(EFF) during periods of persistent antigenic stimulation is based on a program that has two sequential phases of clonal expansion: an initial stage that occurs mainly in the secondary lymphoid tissues and is mediated by ligation of the T cell receptor (TCR) and CD27, and a subsequent, IL-2-dependent phase that occurs predominantly in peripheral, nonlymphoid tissues. The TCR/CD27-dependent phase establishes a nondifferentiating, self-renewing pool of clonally expanding cells, and the IL-2-dependent phase mediates continued clonal expansion that is coupled to the development of T(EFF). The two pools are linked by the process of asymmetrical division within the self-renewing subset so that, at steady state of cellular replication in this TCR/CD27-dependent subset, one daughter cell remains undifferentiated and the other initiates its commitment to IL-2-dependent terminal differentiation. Superimposed on this basic scheme are a shift in the CD8(+) T cell response to type I and II interferon (IFN) from anti- to pro-proliferative and transcriptional control of replicative senescence by Bmi-1, Blimp-1, and BCL6/BCL6b. This developmental program ensures that despite the occurrence of cellular senescence antiviral CD8(+) T cell clones are maintained for the duration of persistent viral infections.
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PMID:The expansion and maintenance of antigen-selected CD8(+) T cell clones. 1798 Dec 5