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Biological Research

Print version ISSN 0716-9760

Abstract

VISSE, EDWARD; INOSTROZA, JUAN; CABELLO, GERTRUDIS  and  PARRA, EDUARDO. The MAP Kinases are Differently Utilized by CD28 and CD2 Adhesion Pathways in Superantigen-Activated Jurkat T cells. Biol. Res. [online]. 2003, vol.36, n.2, pp.263-278. ISSN 0716-9760.  http://dx.doi.org/10.4067/S0716-97602003000200016.

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-g 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-g 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.

Keywords : CD28 response element; Staphylococcal Enterotoxin A-E; Extracellular signal regulated kinase; c-Jun N-terminal kinase; Interleukin-2.

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