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Antigen Persistence Is Required for Dendritic Cell Licensing and CD8⁺ T Cell Cross-Priming¹

Hélène Jusforgues-Saklani^*,, Martin Uhl^*,, Nathalie Blachère^*, Fabrice Lemaître^*, Olivier Lantz, Philippe Bousso^*, Deborah Braun^*,, James J. Moon and Matthew L. Albert^2,*,

^* Immunology Department, Institut Pasteur, Institut Curie, Institut National de la Santé et de la Recherche Médicale Unité 818, Paris France; and Department of Immunology, University of Minnesota, MN 55455

It has been demonstrated that CD4⁺ T cells require Ag persistence to achieve effective priming, whereas CD8⁺ T cells are on "autopilot" after only a brief exposure. This finding presents a disturbing conundrum as it does not account for situations in which CD8⁺ T cells require CD4⁺ T cell help. We used a physiologic in vivo model to study the requirement of Ag persistence for the cross-priming of minor histocompatibility Ag-specific CD8⁺ T cells. We report inefficient cross-priming in situations in which male cells are rapidly cleared. Strikingly, the failure to achieve robust CD8⁺ T cell activation is not due to a problem with cross-presentation. In fact, by providing "extra help" in the form of dendritic cells (DCs) loaded with MHC class II peptide, it was possible to achieve robust activation of CD8⁺ T cells. Our data suggest that the "licensing" of cross-presenting DCs does not occur during their initial encounter with CD4⁺ T cells, thus accounting for the requirement for Ag persistence and suggesting that DCs make multiple interactions with CD8⁺ T cells during the priming phase. These findings imply that long-lived Ag is critical for efficient vaccination protocols in which the CD8⁺ T cell response is helper-dependent.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by grants from Mildred Scheel Stipendium Deutsche Krebshilfe e.V. (to M.U.), La Ligue Nationale Contre le Cancer, L’Agencé Nationale de la Récherche, and The European Young Investigator Awards Scheme, European Science Foundation (to M.L.A.).

² Address correspondence and reprint requests to Dr. Matthew L. Albert, Institut Pasteur, 25 rue du Dr. ROUX, Paris 75724, France. E-mail address: albertm{at}pasteur.fr

³ Abbreviations used in this paper: DC, dendritic cell; CFDA-SE, carboxyfluorescein diacetate succinimidyl ester; β₂m, β₂-microglobulin; DLN, draining lymph node; SFC, spot forming cell; WT, wild type.

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