T cell adhesion lowers the threshold for antigen detection

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Abstract
Antigen detection and initiation of TCR signaling only occur, under physiological conditions, when T cells are adherent, and not in suspension. We show here that T cell adhesion causes an increase in the Ca2+ content of intracellular stores and of the amount of phosphatidylinositol 4,5-bisphosphate in the plasma membrane, and enhances TCR-induced Ca2+ signaling. This priming can be observed in freshly isolated T cells, in activated T cells, and in some T cell lines. Stimulation of T cells by specific monomeric MHC-peptide complexes only triggers Ca2+ responses after T cell adhesion. This solves a controversial issue concerning the minimum valency of activatory TCR ligands. Adhesion-induced T cell priming not only occurs upon binding to artificial substrates such as immobilized ligands, but also upon interaction with dendritic cells. Thus, this phenomenon is likely to contribute to the high sensitivity of antigen detection by T cells in secondary lymphoid organs.