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Development of a CD28 Receptor Binding-Based Screen and Identification of a Biologically Active Inhibitor

✍ Scribed by Chung-Her Jenh; Meng Zhang; Maria Wiekowski; Jimmy C. Tan; Xue-Dong Fan; Vinod Hegde; Mahesh Patel; Robert Bryant; Satwant K. Narula; Paul J. Zavodny; Chuan-Chu Chou

Publisher: Elsevier Science
Year: 1998
Tongue: English
Weight: 152 KB
Volume: 256
Category: Article
ISSN: 0003-2697
DOI: 10.1006/abio.1997.2495

No coin nor oath required. For personal study only.

✦ Synopsis

CD28 is a T-cell costimulatory receptor which plays a pivotal role in antigen-induced T-cell response. We have developed a cell-free and scintillation-proximity assay-based screen to search for molecules that inhibit ligand binding to CD28. The assay was shown to be versatile and adaptable to automation for high-throughput screening. Using this assay, we identified an inhibitor of CD28, NP2214. The inhibitor was shown to be active in vitro by suppressing IL-2 synthesis and proliferation of peripheral blood mononuclear cells in response to CD28 costimulation. We also demonstrated the additive effects of NP2214 and cyclosporine A which act mechanistically distinctly in inhibiting costimulation-induced IL-2 synthesis.

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