Mediated by Reorganization of Membrane Microdomains

Although dispensable, costimulation through CD28 facilitates activation of naı‹ve T lymphocytes. CD28 engagement led to the redistribution and clustering of membrane and intracellular kinase-rich raft microdomains at the site of T cell receptor (TCR) engagements. Although not affecting TCR down-regulation, this process led to higher and more stable tyrosine phosphorylation of several substrates and higher consumption of Lck. These results may provide a general mechanism for amplifying receptor signaling by reorganization of membrane microdomains. The outcome of TCR stimulation is regulated by the simultaneous engagement of the co-stimulatory molecule CD28. Mice lacking CD28 can still mount T cell responses but require repeated stimulations with high doses of antigen (1). In vitro studies demonstrated that in the absence of CD28 engagement, T cells re