On the same side: VISTA and its ligands interact in cis on the cell surface.

ABSTRACT: VISTA, an essential immune checkpoint protein, regulates peripheral T-cell quiescence and tolerance. Despite its potential as a target for anti-tumor and autoimmune disease therapies, uncertainty regarding VISTA's binding mode and membrane orientation has hindered the development of these therapies. Contrary to the prevailing view, we found, using cell aggregation assays, that VISTA does not interact with its ligands in a trans (between-cell) manner. Using MST and flow cytometry, we showed that when in soluble form, VISTA binds to its ligands, suggesting that VISTA's membrane orientation restricts trans interactions. In contrast, split luciferase complementation assays demonstrated that membrane-tethered VISTA interacts with its ligands in a cis manner (i.e., on the same cell). Co-expressi

SUBMITTER: Smorodinsky-Atias K 

PROVIDER: S-EPMC12720419 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature