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Calcium has been implicated as an intracellular messenger in the cellular response to various external stimuli. Exposure of lymphocytes to various mitogens and lectins results in rapid transmembrane calcium fluxes and increased cytoplasmic calcium concentrations ([Ca2+]i). It is not clear, however, whether the mechanisms by which these non-physiological stimuli activate cells are related to those involved in antigen-specific activation. We have now used antigen-specific T-cell clones to study changes in [Ca2+]i associated with specific activation and show here that these cells respond specifically in the presence of antigen and antigen-presenting cells (APC) with increased [Ca2+]i and that this increased [Ca2+]i shows the same genetic restrictions as are seen in the proliferation assay. The kinetics of the [Ca2+]i response to antigen indicate that antigen undergoes a time-dependent processing step as a prerequisite for recognition by T cells, as has been shown for T-cell proliferative responses, but that the [Ca2+]i response to processed antigen is extremely rapid. The close correlation between changes in [Ca2+]i and cell activation resulting in proliferation suggests that Ca2+ may act as an intracellular messenger in antigen-specific responses.

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