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The Interleukin 2 CD28-Responsive Complex Contains at Least Three Members of the NF κB Family: c-Rel, p50, and p65
Paritosh Ghosh, Tse-Hua Tan, Nancy R. Rice, Antonio Sica and Howard A. Young
Proceedings of the National Academy of Sciences of the United States of America
Vol. 90, No. 5 (Mar. 1, 1993), pp. 1696-1700
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/2361384
Page Count: 5
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Optimal activation of T cells requires at least two signals. One signal can be delivered by the antigen-specific T-cell receptor, and the second signal is provided by the costimulatory molecule(s) delivered by the antigen-presenting cell. CD28 is a T-cell surface molecule and stimulation through this protein plays an important role in delivering the second activation signal. In this report, we show that in human peripheral blood T cells, CD28-mediated signal transduction involves the rel family proteins-c-Rel, p50, and p65. Treatment of peripheral blood T cells with phorbol 12-myristate 13-acetate (PMA) and anti-CD28 monoclonal antibody (mAb) results in augmentation of nuclear c-Rel, p50, and p65, and this augmentation can occur in the presence of the immunosupressant cyclosporin A. It is also shown in this report that, in response to PMA/anti-CD28 mAb or anti-CD3/anti-CD28 mAb, c-Rel, p50, and p65 are associated with CD28-responsive element present in the promoter of the human interleukin 2 gene. The functional significance of c-Rel involvement in the CD28-responsive complex is demonstrated by transient transfection analysis, where cotransfection of c-Rel augments the level of expression of a chloramphenicol acetyltransferase reporter gene linked to the CD28-responsive element.
Proceedings of the National Academy of Sciences of the United States of America © 1993 National Academy of Sciences