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, Howard A. Young

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1696-1700
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number5
Publication statusPublished - Mar 1 1993

ASJC Scopus subject areas

  • General
  • Genetics

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