Sustained Antigen Presentation Can Promote an Immunogenic T Cell Response, Like Dendritic Cell Activation

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2007 Sep 21

PMID 17881563

Citations 36

Authors

Reinhard Obst

Hisse-Martien van Santen

Rachel Melamed

Alice O Kamphorst

Christophe Benoist

Diane Mathis

Affiliations

Soon will be listed here.

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.

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