@article{4f9add49128341fb90de221a18ed9c86,
title = "The interchain disulfide linkage is not a prerequisite but enhances CD28 costimulatory function",
abstract = "Oligomeric state makes important contributions to the signaling mechanisms of costimulatory molecules. In this study we address the biological relevance of the disulfide-linked dimeric structure of CD28. Fluorescence Resonance Energy Transfer (FRET) demonstrates that removal of the interdomain disulfide bond (C123) does not interfere with the formation of CD28 oligomers on the cell surface. Although the C123S mutant shows 40% lower binding affinity to the ligand B7-1, it is able to costimulate anti-CD3-induced IL-2 production but at a lower level (150%) compared to the wild-type (270%). Interestingly, binding to B7-2 was not affected. Thus, the covalently linked dimeric structure of CD28 represents an important mechanistic determinant for the optimal costimulatory activity in the immunological synapse.",
keywords = "B7-1, CD28, Costimulatory, Dimer, Disulfide, FRET, Oligomerization",
author = "Eszter Lazar-Molnar and Almo, {Steven C.} and Nathenson, {Stanley G.}",
note = "Funding Information: E.L.-M. was supported by a postdoctoral fellowship from Cancer Research Institute. We thank Sumeena Bhatia for providing the stably transfected CHO-B7-1 cell line and the B7-1-CFP-YFP expression plasmid; we acknowledge Sanchari Bhattacharya{\textquoteright}s contributions to this project. We thank the Analytical Imaging Facility at Albert Einstein College of Medicine and especially Michael Cammer; the Flow Cytometry Facility supported by the grant of the National Cancer Institute{\textquoteright}s cancer center (P30CA013330) and especially William King; Fernando Macian and Olga Ujhelly for help with the retroviral infection; Teresa DiLorenzo, Fernando Macian and Kausik Chattopadhyay for critically reviewing the manuscript. This work was supported by National Institutes of Health Grant AI07289 (to S.G.N.). ",
year = "2006",
month = dec,
doi = "10.1016/j.cellimm.2007.02.014",
language = "English (US)",
volume = "244",
pages = "125--129",
journal = "Cellular Immunology",
issn = "0008-8749",
publisher = "Academic Press Inc.",
number = "2",
}