INVOLVEMENT OF REL, FOS, AND JUN PROTEINS IN BINDING-ACTIVITY TO THE IL-2 PROMOTER CD28 RESPONSE ELEMENT AP-1 SEQUENCE IN HUMAN T-CELLS

CD28 is an important costimulatory molecule in the activation of human T cells, Costimulation of T cells through both the Ag receptor and CD 28 leads to high level IL-2 production, which is vital to the developm ent of an immune response in vivo, Previous reports have suggested the CD28 stimulation contributes to the activation of the IL-2 promoter b y up-regulating the activity of several transcription factors, includi ng AP-1 and nuclear factor-kappa B (NF-kappa B)/Rel family members as well as an uncharacterized transcription factor called CD28 response c omplex, While several lines of investigation have suggested that NF-ka ppa B/Rel family members make up the CD28 response complex transcripti on factor, other work has not supported this conclusion, Recent studie s suggest that the CD28 response element (CD28RE) does not function in dependently but works instead in conjunction with the adjacent promote r proximal AP-1-binding site and this hypothesis is confirmed here, Al so in the current study, binding activity to the CD28RE/AP-1 sequence of the IL-2 promoter is evaluated, Although four specific complexes ca n be detected binding to this sequence, only one of these complexes is specific for both the CD28RE and the adjacent AP-1 site, Of the NF-ka ppa B/Rel family members tested, this CD28RE/AP-1-specific complex con tains predominantly c-Rel, despite the fact that both p50 and RelA can efficiently bind to the CD28RE, c-Fos and c-jun are also found in thi s CD28RE/AP-1-specific complex, These data indicate that functional co mplexes encompassing both the CD28RE and the AP-1-binding sites influe nce IL-2 promoter activity in CD28-costimulated T cells.