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Sialic Acid Ligands of CD28 Suppress Costimulation of T Cells.

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, costimulation 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 costimulation. Removal of sialic acids enhances antigen-mediated activation of naïve T cells and also increases the revival of effector T cells made hypofunctional or exhausted via chronic viral infection. This occurs through a mechanism that is synergistic with antibody blockade of the inhibitory PD-1 axis. These results reveal a previously unrecognized role of sialic acid ligands in attenuation of CD28-mediated costimulation of T cells.

SUBMITTER: Edgar LJ

PROVIDER: S-EPMC8461770 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Sialic Acid Ligands of CD28 Suppress Costimulation of T Cells.

Edgar Landon J LJ Thompson Andrew J AJ Vartabedian Vincent F VF Kikuchi Chika C Woehl Jordan L JL Teijaro John R JR Paulson James C JC

ACS central science 20210823 9

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, costimulation 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 costimulation. Removal of sialic acids enhances ant ...[more]

PMID: 34584952

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