title: A proteomic view at T cell costimulation.
abstract: The "two-signal paradigm" in T cell activation predicts that the cooperation of "signal 1," provided by the T cell receptor (TCR) through engagement of major histocompatility complex (MHC)-presented peptide, with "signal 2″ provided by costimulatory molecules, the prototype of which is CD28, is required to induce T cell effector functions. While the individual signalling pathways are well understood, little is known about global changes in the proteome pattern during TCR/CD28-mediated activation. Therefore, comparative 2-DE-based proteome analyses of CD3(+) CD69(-) resting T cells versus cells incubated with (i) the agonistic anti-CD3 antibody OKT3 mimicking signal 1 in absence or presence of IL-2 and/or with (ii) the agonistic antibody 15E8 triggering CD28-mediated signaling were performed. Differentially regulated spots were defined leading to the identification of proteins involved in the regulation of the metabolism, shaping and maintenance of the cytoskeleton and signal transduction. Representative members of the differentially expressed protein families, such as calmodulin (CALM), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), L-lactate dehydrogenase (LDH), Rho GDP-dissociation inhibitor 2 (GDIR2), and platelet basic protein (CXCL7), were independently verified by flow cytometry. Data provide a detailed map of individual protein alterations at the global proteome level in response to TCR/CD28-mediated T cell activation.
authors.affiliation: Institute of Medical Immunology, Martin-Luther-University Halle-Wittenberg, Halle, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Lichtenfels
authors.forename: Gunter
authors.initials: G
authors.lastname: Rappl
authors.forename: Andreas A
authors.initials: AA
authors.lastname: Hombach
authors.forename: Christian V
authors.initials: CV
authors.lastname: Recktenwald
authors.forename: Sven P
authors.initials: SP
authors.lastname: Dressler
authors.forename: Hinrich
authors.initials: H
authors.lastname: Abken
authors.forename: Barbara
authors.initials: B
authors.lastname: Seliger
mesh_terms: D000906:Antibodies / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D018106:CD28 Antigens / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D003599:Cytoskeleton; D015180:Electrophoresis, Gel, Two-Dimensional; D005434:Flow Cytometry; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D008213:Lymphocyte Activation; D016853:Muromonab-CD3 / Q000276:immunology / Q000378:metabolism; D020543:Proteome / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D000099192:CD69 Antigens
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D017252:CD3 Complex; D007376:Interleukin-2; D037181:Lectins, C-Type; D016853:Muromonab-CD3; D020543:Proteome; D011948:Receptors, Antigen, T-Cell; D000099192:CD69 Antigens