Abstract
CD28 is a cell surface glycoprotein expressed on T cells that modulates immune responses through its ability to transduce costimulatory signals. Even though nearly 50% of the molecular mass of CD28 is N-glycan, the physiological significance of CD28 glycosylation is at present unknown. In this report, we have investigated the function of hypoglycosylated wildtype CD28 and its splice variant, CD28i. When N-glycosylation was prevented through point mutations in N-glycosylation sites in CD28, or reduced by glycosidase inhibitors, the binding of CD28 to CD80 significantly increased. Stimulation of hypoglycosylated CD28 induced IL-2 promoter activity greater than that induced through the stimulation of wildtype CD28. Unlike hypoglycosylated wildtype CD28, hypoglycosylation of CD28i did not alter CD28i functions. Our data indicate that N-glycans of CD28 negatively regulate CD28/CD80 interactions, resulting in diminished CD28 signaling. It is also suggested that N-glycans regulate the density of CD28 clustering upon ligation with CD80/CD86. The results support the hypothesis that the N-glycosylation negatively regulates CD28-mediated T cell adhesion and costimulation.
Original language | English |
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Pages (from-to) | 60-67 |
Number of pages | 8 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 317 |
Issue number | 1 |
DOIs | |
Publication status | Published - Apr 23 2004 |
Externally published | Yes |
Bibliographical note
Funding Information:We thank Dr. C. Rudd (Harvard Medical School, Boston MA), Dr. S.-C. Sun (Pennsylvania state U., Hershey PA), and Dr. T.H. Watts (Toronto U, Toronto ON) for their generous gifts of cell lines and reagents. This work was supported by grants from the Canadian Institutes of Health Research CIHR (MT-15481) and Multi-Organ Transplant Program.
ASJC Scopus Subject Areas
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology