Local changes in lipid environment of TCR microclusters regulate membrane binding by the CD3? cytoplasmic domain.

ABSTRACT: The CD3? and ? cytoplasmic domains of the T cell receptor bind to the inner leaflet of the plasma membrane (PM), and a previous nuclear magnetic resonance structure showed that both tyrosines of the CD3? immunoreceptor tyrosine-based activation motif partition into the bilayer. Electrostatic interactions between acidic phospholipids and clusters of basic CD3? residues were previously shown to be essential for CD3? and ? membrane binding. Phosphatidylserine (PS) is the most abundant negatively charged lipid on the inner leaflet of the PM and makes a major contribution to membrane binding by the CD3? cytoplasmic domain. Here, we show that TCR triggering by peptide--MHC complexes induces dissociation of the CD3? cytoplasmic domain from the plasma membrane. Release of the CD3? cytoplasmic domain from the membrane is accompanied by a substantial focal reduction in negative charge and available PS in TCR microclusters. These changes in the lipid composition of TCR microclusters even occur when TCR signaling is blocked with a Src kinase inhibitor. Local changes in the lipid composition of TCR microclusters thus render the CD3? cytoplasmic domain accessible during early stages of T cell activation.

SUBMITTER: Gagnon E 

PROVIDER: S-EPMC3526357 | biostudies-other | 2012 Dec

REPOSITORIES: biostudies-other