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  • Title: Co-stimulation and counter-stimulation: lipid raft clustering controls TCR signaling and functional outcomes.
    Author: Miceli MC, Moran M, Chung CD, Patel VP, Low T, Zinnanti W.
    Journal: Semin Immunol; 2001 Apr; 13(2):115-28. PubMed ID: 11308295.
    Abstract:
    T cell receptor (TCR) antigen recognition induces the formation of a specialized 'immunological synapse' at the T cell : antigen presenting cell (APC) junction. This junction is generated by the recruitment and exclusion of particular proteins from the contact area and is required for T cell activation. We and others have hypothesized that lipid raft/non-raft partitioning provides a molecular basis for protein sorting which organizes the TCR, co-stimulators, signal transducers and the actin cytoskeleton at the T cell : APC interface. Here we discuss the emerging paradigm that co-stimulators induce the directional transport and clustering of lipid rafts at the T cell : APC interface, thus generating platform(s) specialized for processive and sustained TCR signal transduction and T cell activation. We also discuss recent data implicating the involvement of 'counter-stimulators' and other negative regulators which prevent optimal raft clustering at the TCR contact site and, thus, facilitate T cell inactivation and tolerance induction.
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