Cis-B7:CD28 interactions at invaginated synaptic membranes provide CD28 co-stimulation and promote CD8⁺ T cell function and anti-tumor immunity.

ABSTRACT: B7 ligands (CD80 and CD86), expressed by professional antigen-presenting cells (APCs), activate the main co-stimulatory receptor CD28 on T cells in trans. However, in peripheral tissues, APCs expressing B7 ligands are relatively scarce. This raises the questions of whether and how CD28 co-stimulation occurs in peripheral tissues. Here, we report that CD8⁺ T cells displayed B7 ligands that interacted with CD28 in cis at membrane invaginations of the immunological synapse as a result of membrane remodeling driven by phosphoinositide-3-kinase (PI3K) and sorting-nexin-9 (SNX9). cis-B7:CD28 interactions triggered CD28 signaling through protein kinase C theta (PKCθ) and promoted CD8⁺ T cell survival, migration, and cytokine production. In mouse tumor models, loss of T cell-

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC10330546 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature