Sustained antigen presentation can promote an immunogenic T cell response, like dendritic cell activation

Reinhard Obst, Hisse Martien Van Santen, Rachel Melamed, Alice O. Kamphorst, Christophe Benoist, Diane Mathis

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Activation of dendritic cells (DCs) enhances their ability to prime naïve T cells. How activation renders them immunogenic rather than tolerogenic is unclear. Here, we show, using temporally regulated expression of a transgene-encoded neoself antigen in DCs, that either prolonged antigen presentation or DC activation could elicit full expansion, effector cytokine production, and memory-cell differentiation. Microarray analysis of gene expression in T cells showed that all changes linked to DC activation through CD40 could be reproduced by persistent antigen delivery, suggesting that stabilization of antigen presentation is an important consequence of DC activation in vivo. In this system, DC activation by CD40 engagement indeed extended their ability to present antigen to CD4+ T cells in vivo, although different results were obtained with antigen delivered to DCs by means of endocytosis from the cell surface. These results suggest that antigen persistence may be an important discriminator of immunogenic and tolerogenic antigen exposure.

Original languageEnglish
Pages (from-to)15460-15465
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number39
DOIs
StatePublished - 25 Sep 2007
Externally publishedYes

Keywords

  • Immune response
  • Immune tolerance
  • MHC class II
  • Regulated transgene

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