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      Impaired T Cell Proliferation and Zeta Chain Phosphorylation after Stimulation with Staphylococcal Enterotoxin-B in Hemodialysis Patients

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          Background: Patients on regular hemodialysis treatment are in an immunodeficiency state. Several studies have shown defective T cell proliferation after stimulation with various agents. Staphylococcal enterotoxin B (SEB) is a MHC-dependent superantigen that triggers proliferation of a large proportion of T cells. T cell activation after stimulation with SEB parallels normal T cell signal transduction. An important and early event in this transduction pathway is the phosphorylation of the ζ chain. In this study, T cell proliferation and ζ chain phosphorylation after stimulation with SEB were evaluated. Methods: Peripheral blood mononuclear cells (PBMCs) from 24 patients and 14 healthy individuals were isolated and cultured with or without stimulation with SEB (1 ng/ml). Cell proliferation was estimated by immunoenzymatic measurement of bromodeoxyuridine uptake. PBMCs from 8 patients and 6 healthy individuals were isolated and pulsed for 2 min with or without SEB (10 µg/ml). ζ chain phosphorylation was estimated by immunoprecipitation and immunoblotting with antiphosphotyrosine antibody. Results: Lymphocyte proliferation index after SEB stimulation was lower in hemodialyzed patients. Stimulation of T cells with SEB also resulted in a lower ζ chain phosphorylation in hemodialyzed patients. Conclusions: Lymphocyte proliferation after MHC-dependent stimulation is impaired in hemodialyzed patients. This proliferation defect is due to impaired ζ chain phosphorylation.

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          Most cited references 15

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          CD28/B7 system of T cell costimulation.

          T cells play a central role in the initiation and regulation of the immune response to antigen. Both the engagement of the TCR with MHC/Ag and a second signal are needed for the complete activation of the T cell. The CD28/B7 receptor/ligand system is one of the dominant costimulatory pathways. Interruption of this signaling pathway with CD28 antagonists not only results in the suppression of the immune response, but in some cases induces antigen-specific tolerance. However, the CD28/B7 system is increasingly complex due to the identification of multiple receptors and ligands with positive and negative signaling activities. This review summarizes the state of CD28/B7 immunobiology both in vitro and in vivo; summarizes the many experiments that have led to our current understanding of the participants in this complex receptor/ligand system; and illustrates the current models for CD28/B7-mediated T cell and B cell regulation. It is our hope and expectation that this review will provoke additional research that will unravel this important, yet complex, signaling pathway.
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            Capture and processing of exogenous antigens for presentation on MHC molecules.

             Joel Watts (1996)
            Class I and class II MHC molecules bind peptides during their biosynthetic maturation and provide a continuously updated display of intracellular and environmental protein composition, respectively, for scrutiny by T cells. Receptor-mediated endocytosis, phagocytosis, and macropinocytosis all contribute to antigen uptake by class II MHC-positive antigen-presenting cells. Capture of antigenic peptides by class II MHC molecules is facilitated because antigen catabolism and class II MHC maturation take place in the same compartments or in communicating compartments of the endosome/lysosome system. These class II MHC-rich, multivesicular endosomes receive incoming antigen and can support not only antigen processing and class II MHC peptide loading but also the export of peptide/class II MHC complexes to the cell surface. A balance between production and destruction of antigenic peptides is achieved by the activity of local proteases and may be influenced by binding of antigen to other proteins both prior to the onset of processing (e.g. antibodies) and during antigen unfolding (e.g. MHC molecules). T cell determinants that can be released for MHC binding without a substantial processing requirement may be able to utilize a distinct minor population of cell surface class II MHC molecules that become available during peripheral recycling. Although peptides derived from exogenous protein sources are usually excluded from presentation on class I MHC molecules, recent evidence shows that this embargo may be lifted in certain professional antigen-presenting cells to increase the spectrum of antigens that may be displayed on class I MHC.
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              The dynamics of T cell receptor signaling: complex orchestration and the key roles of tempo and cooperation.

              T cells constantly sample their environment using receptors (TCR) that possess both a germline-encoded low affinity for major histocompatibility complex (MHC) molecules and a highly diverse set of CDR3 regions contributing to a range of affinities for specific peptides bound to these MHC molecules. The decision of a T cell "to sense and to respond" with proliferation and effector activity rather than "to sense, live on, but not respond" is dependent on TCR interaction with a low number of specific foreign peptide:MHC molecule complexes recognized simultaneously with abundant self peptide-containing complexes. Interaction with self-complexes alone, on the other hand, generates a signal for survival without a full activation response. Current models for how this distinction is achieved are largely based on translating differences in receptor affinity for foreign versus self ligands into intracellular signals that differ in quality, intensity, and/or duration. A variety of rate-dependent mechanisms involving assembly of molecular oligomers and enzymatic modification of proteins underlie this differential signaling. Recent advances have been made in measuring TCR:ligand interactions, in understanding the biochemical origin of distinct proximal and distal signaling events resulting from TCR binding to various ligands, and in appreciating the role of feedback pathways. This new information can be synthesized into a model of how self and foreign ligand recognition each evoke the proper responses from T cells, how these two classes of signaling events interact, and how pathologic responses may arise as a result of the underlying properties of the system. The principles of signal spreading and stochastic resonance incorporated into this model reveal a striking similarity in mechanisms of decision-making among T cells, neurons, and bacteria.

                Author and article information

                Nephron Clin Pract
                Nephron Clinical Practice
                S. Karger AG
                January 2004
                17 November 2004
                : 96
                : 1
                : c15-c20
                aDepartment of Nephrology, B’ IKA Hospital; bLaboratory of Research, Anticancer Hospital, Thessaloniki, and cLaboratory of Biochemistry, and dDepartment of Nephrology, Demokritus University of Thrace, Alexandroupolis, Greece
                75567 Nephron Clin Pract 2004;96:c15–c20
                © 2004 S. Karger AG, Basel

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                Page count
                Figures: 3, References: 49, Pages: 1
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/75567
                Original Paper


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