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The initiation of an immune response requires that professional antigen-presenting cells, such as dendritic cells, physically interact with antigen-specific T cells within the complex environment of the lymph node. Although the way in which antigen is presented to T cells and in particular the cellular associations involved in antigen-specific stimulation events have been extensively investigated, data on antigen presentation have come primarily from studies in vitro or examination of the late consequences of antigen presentation in vivo. However, there is increasing recognition that events defined in vitro might not correspond entirely to the physiological situation in vivo. Recent developments in imaging technology now allow real-time observation of single-cell and molecular interactions in intact lymphoid tissues and have already contributed to a more detailed picture of how cells coordinate the initiation or suppression of an immune response.