Journal
IMMUNITY
Volume 15, Issue 6, Pages 921-933Publisher
CELL PRESS
DOI: 10.1016/S1074-7613(01)00248-5
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Funding
- PHS HHS [A139021] Funding Source: Medline
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Since CD28 provides cosignals in T cell responses, a key question is whether the coreceptor operates exclusively via TCR zeta /CD3 or also operates as an independent signaling unit. In this study, we show that CD28 can cooperate with VAV/SLP-76 adaptors to upregulate interleukin 2/4 transcription independently of TCR ligation. CD28 signaling is dependent on VAV/ SLP-76 complex formation and induces membrane localization of these complexes. CD28-VAV/SLP-76 also functions in nonlymphoid cells to promote nuclear entry of NFAT, indicating that these adaptors are the only lymphoid components needed for this pathway. Further downstream, CD28-VAV/SLP-76 synergizes with Rac1 and causes F-actin remodelling proximal to receptor. Autonomous CD28 signaling may account for the distinct nature of the second signal and in trans amplification of T cell responses.
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