The plasma membrane of mammalian cells contains detergent-resistant me
mbrane rafts enriched in glycosphingolipids and cholesterol. Although
several important signaling molecules have been found in such rafts, e
vidence documenting a functional role for their localization has been
scarce. Using a fractionation scheme that preserves tyrosine phosphory
lation, we show that T cell activation leads to a striking compartment
ation in the rafts of activated T cell receptor and associated signal-
transducing molecules. Conditions that reversibly disrupt raft structu
re either by dispersing their contents or by forcing their internaliza
tion reversibly disrupt the earliest steps of T cell activation. Thus,
raft integrity is a prerequisite for efficient T cell receptor signal
transduction.