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Jérôme Delon^*, Nadège Bercovici^*,, Graça Raposo, Roland Liblau^*,, and Alain Trautmann^*

From the ^* Laboratoire d'Immunologie Cellulaire, Centre National de la Recherche Scientifique UMR 7627, CERVI, 75013 Paris, France; the INSERM CJF 96-08, Hôpital de la Pitié-Salpêtrière, 75013 Paris, France; and the Laboratoire de Microscopie Électronique des Compartiments Cellulaires, Institut Curie, Section de Recherche, Centre National de la Recherche Scientifique UMR 144, 75005 Paris, France

Dendritic cells (DCs) are much more potent antigen (Ag)-presenting cells than resting B cells for the activation of naive T cells. The mechanisms underlying this difference have been analyzed under conditions where ex vivo DCs or B cells presented known numbers of specific Ag–major histocompatibility complex (MHC) complexes to naive CD4⁺ T cells from T cell antigen receptor (TCR) transgenic mice. Several hundred Ag–MHC complexes presented by B cells were necessary to elicit the formation of a few T–B conjugates with small contact zones, and the resulting individual T cell Ca²⁺ responses were all-or-none. In contrast, Ag-specific T cell Ca²⁺ responses can be triggered by DCs bearing an average of 30 Ag–MHC complexes per cell. Formation of T–DC conjugates is Ag-independent, but in the presence of the Ag, the surface of the contact zone increases and so does the amplitude of the T cell Ca²⁺ responses. These results suggest that Ag is better recognized by T cells on DCs essentially because T–DC adhesion precedes Ag recognition, whereas T–B adhesion requires Ag recognition. Surprisingly, we also recorded small Ca²⁺ responses in T cells interacting with unpulsed DCs. Using DCs purified from MHC class II knockout mice, we provide evidence that this signal is mostly due to MHC–TCR interactions. Such an Ag-independent, MHC-triggered calcium response could be a survival signal that DCs but not B cells are able to deliver to naive T cells.

Key Words: dendritic cells • B cells • T cells • Ca²⁺ imaging • contact zone

Abbreviations used: [Ca²⁺]_i, intracellular calcium concentration; DC, dendritic cell; HA, hemagglutinin; MFI, mean fluorescence intensity; Tg, transgenic.

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