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We investigated the functional role of large-scale molecular segregation at the T cell-APC contact site during T lymphocyte Ag recognition. Inhibition of CD2-CD58 interaction markedly affected segregation of CD2 and CD2AP from CD45. Under these conditions, Ag-induced calcium mobilization, PKC theta; clustering at the immunological synapse, and IFN-gamma production also were inhibited. However, early TCR signaling and T cell polarization toward APCs were unaffected. Our results indicate that the "raison d'être" of a large-scale segregation of surface molecules and intracellular enzymes and adapters, in Ag-stimulated T cells, is to reinforce the assembly of the signal transduction cascade rather than favor TCR engagement and triggering.

Cutting Edge: TCR Engagement and Triggering in the Absence of Large-Scale Molecular Segregation at the T Cell-APC Contact Site