Sialic acid ligands of CD28 block co-stimulation of T cells
Edgar, L. J.; Thompson, A. J.; Vartabedian, V. F.; Kikuchi, C.; Woehl, J. L.; Teijaro, J. R.; Paulson, J. C.
Show abstract
Effector T cells comprise the cellular arm of the adaptive immune system and are essential for mounting immune responses against pathogens and cancer. To reach effector status, co-stimulation through CD28 is required. Here, we report that sialic acid-containing glycans on the surface of both T cells and APCs are alternative ligands of CD28 that compete with binding to its well-documented activatory ligand CD80 on the APC, resulting in attenuated co-stimulation. Removal of sialic acids enhances T cell activation and enhances the activity of effector T cells made hypofunctional via chronic viral infection through a mechanism that is synergistic with antibody blockade of the inhibitory PD-1 axis. These results reveal a previously unrecognized role for sialic acids in attenuation of CD28 mediated co-stimulation of T cells. One Sentence SummarySialic acids attenuate the second signal required for T cell activation.
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