The MAP kinases are differently utilized by CD28 and CD2 adhesion pathways in superantigen-activated Jurkat T cells.
To mimic the two-signal requirements for T cell activation mediated by ligands, we exposed the superantigens SEA or SEE (signal 1) to T cells incubated with HLA-DR/LFA-3 or HLA-DR/B7-1-CHO transfected cells (signal 2). LFA-3 costimulation was able to induce T cell proliferation as well as IFN-gamma and IL-4 production at similar levels as in cells induced by B7-1. Analysis of the CD28RE of the IL-2 promoter showed specific transcription factor recruitment at the CD28RE element upon induction by B7-1/SEE. Further functional studies with an IL-2 enhancer-promoter carrying either wild type or mutated versions of the CD28RE site revealed that this element is necessary for full activation upon B7-1 costimulation. While both CD28/B7-1 and CD2/LFA-3 costimulation resulted in the up-regulation of IL-4 and IFN-gamma promoters, IL-2 promoter activity and production of IL-2 were only seen after B7-1 costimulation. However, contrary to what has been previously proposed, we show that costimulation with either B7-1 or LFA-3 further enhanced the ERK-2 activity and strongly activated the p38 MAPK pathway, but only B7-1 costimulation induced high levels of JNK-1 activity. These data suggest that the differential effect of CD28 vs. CD2 can be related to the difference in the ability of the two pathways to induce JNK-1 activity.
D000818:Animals; D018122:B7-1 Antigen / Q000494:pharmacology; D018801:CD2 Antigens / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology; D018968:CD58 Antigens / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D004768:Enterotoxins / Q000276:immunology*; D004789:Enzyme Activation; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D019169:Jurkat Cells / Q000276:immunology* / Q000502:physiology; D008213:Lymphocyte Activation; D048670:MAP Kinase Kinase 4; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases
D018122:B7-1 Antigen; D018801:CD2 Antigens; D018106:CD28 Antigens; D018968:CD58 Antigens; D004768:Enterotoxins; D007376:Interleukin-2; C049463:enterotoxin E, Staphylococcal; C026066:enterotoxin A, Staphylococcal; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases