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.

doi:10.1101/2021.02.22.432333

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bioRxiv · 10.1101/2021.02.22.432333

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.

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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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Edgar, L. J., Thompson, A. J., Vartabedian, V. F., Kikuchi, C., Woehl, J. L., Teijaro, J. R., Paulson, J. C.. 2021-02-22. Sialic acid ligands of CD28 block co-stimulation of T cells. https://doi.org/10.1101/2021.02.22.432333

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