CD28 responsiveness within the IL-2 promoter is conferred by a composite element containing the CD28RE and the adjacent NF-IL-2B AP-1 site ("RE/AP"). To determine the role of the RE/AP composite element to IL-2 promoter activation in response to a physiological stimulus, the superantigen SED was used. The incubation of Jurkat T cells with the superantigen SED presented by RAJI B cells activates reporters containing either RE/AP, NFAT, AP-1 or the IL-2 promoter, as well as surface expression of CD69. CTLA-4-Ig was used to block CD28 activation, and determine the contribution of CD28 signalling in this system. The activation of the IL-2 promoter in response to superantigen is blocked by the addition of CTLA-4-Ig. Interestingly, no effect is observed on CD69 expression, or the activation of the NFAT or AP-1 reporters. However, the activation of the RE/AP reporter is also blocked by CTLA-4-Ig. Therefore, RE/AP, but not NFAT or AP-1, appears to be the target within the IL-2 promoter that is blocked upon CTLA-4-Ig incubation. Additionally, FK506 could also block activation of RE/AP in response to superantigen. Therefore, RE/AP is a site of signal integration requiring both TCR and CD28 derived signals.
|Original language||English (US)|
|State||Published - Mar 20 1998|
ASJC Scopus subject areas
- Molecular Biology