B7/CD28 costimulation of T cells induces a distinct proteome pattern.
Effective immune strategies for the eradication of human tumors require a detailed understanding of the interaction of tumor cells with the immune system, which might lead to an optimization of T cell responses. To understand the impact of B7-mediated costimulation on T cell activation comprehensive proteome analysis of B7-primed T cell populations were performed. Using this approach we identified different classes of proteins in T cells whose expression is either elevated or reduced upon B7-1- or B7-2-mediated CD28 costimulation. The altered proteins include regulators of the cell cycle and cell proliferation, signal transducers, components of the antigen processing machinery, transporters, cytoskeletal proteins, and metabolic enzymes. A number of differentially expressed proteins are further modified by phosphorylation. Our results provide novel insights into the complexity of the CD28 costimulatory pathway of T cells and will help to identify potential targets of therapeutic interventions for modulating anti-tumor T cell activation.
Kronfeld
Kai
K
IIIrd Department of Internal Medicine, Johannes Gutenberg University, 55131 Mainz, Germany.
Hochleitner
Elisabeth
E
Mendler
Simone
S
Goldschmidt
Jutta
J
Lichtenfels
Rudolf
R
Lottspeich
Friedrich
F
Abken
Hinrich
H
Seliger
Barbara
B
D015703:Antigens, CD / Q000276:immunology*; D001483:Base Sequence; D001798:Blood Proteins / Q000302:isolation & purification; D018106:CD28 Antigens / Q000276:immunology*; D002292:Carcinoma, Renal Cell; D045744:Cell Line, Tumor; D017931:DNA Primers; D015180:Electrophoresis, Gel, Two-Dimensional; D005786:Gene Expression Regulation; D015789:HLA-A2 Antigen / Q000097:blood; D006801:Humans; D007680:Kidney Neoplasms; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D013058:Mass Spectrometry; D010750:Phosphoproteins / Q000235:genetics / Q000302:isolation & purification; D020543:Proteome / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D001798:Blood Proteins; D018106:CD28 Antigens; D017931:DNA Primers; D015789:HLA-A2 Antigen; D010750:Phosphoproteins; D020543:Proteome