The Journal of Experimental Medicine
Avanti Polar Lipids, Inc.
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 16 December 2002. doi:10.1084/jem.20021598
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 388K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bonifaz, L.
Right arrow Articles by Steinman, R. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bonifaz, L.
Right arrow Articles by Steinman, R. M.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© Rockefeller University Press, 0022-1007/2002/12/1627/ $5.00
The Journal of Experimental Medicine, Volume 196, Number 12, December 16, 2002 1627-1638

Efficient Targeting of Protein Antigen to the Dendritic Cell Receptor DEC-205 in the Steady State Leads to Antigen Presentation on Major Histocompatibility Complex Class I Products and Peripheral CD8+ T Cell Tolerance

Laura Bonifaz1, David Bonnyay1, Karsten Mahnke1,4, Miguel Rivera1, Michel C. Nussenzweig2,3 and Ralph M. Steinman1,3

1 Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021
2 Laboratory of Molecular Immunology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021
3 Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY 10021
4 Department of Dermatology, University of Mainz, D-55101 Mainz, Germany

Address correspondence to Ralph M. Steinman, Laboratory for Cellular Physiology and Immunology, The Rockefeller University, 1230 York Ave., Box 176, New York, NY 10021. Phone: 212-327-8106; Fax: 212-327-8875; E-mail: Steinma{at}mail.rockefeller.edu

To identify endocytic receptors that allow dendritic cells (DCs) to capture and present antigens on major histocompatibility complex (MHC) class I products in vivo, we evaluated DEC-205, which is abundant on DCs in lymphoid tissues. Ovalbumin (OVA) protein, when chemically coupled to monoclonal {alpha}DEC-205 antibody, was presented by CD11c+ lymph node DCs, but not by CD11c- cells, to OVA-specific, CD4+ and CD8+ T cells. Receptor-mediated presentation was at least 400 times more efficient than unconjugated OVA and, for MHC class I, the DCs had to express transporter of antigenic peptides (TAP) transporters. When {alpha}DEC-205:OVA was injected subcutaneously, OVA protein was identified over a 4–48 h period in DCs, primarily in the lymph nodes draining the injection site. In vivo, the OVA protein was selectively presented by DCs to TCR transgenic CD8+ cells, again at least 400 times more effectively than soluble OVA and in a TAP-dependent fashion. Targeting of {alpha}DEC-205:OVA to DCs in the steady state initially induced 4–7 cycles of T cell division, but the T cells were then deleted and the mice became specifically unresponsive to rechallenge with OVA in complete Freund's adjuvant. In contrast, simultaneous delivery of a DC maturation stimulus via CD40, together with {alpha}DEC-205:OVA, induced strong immunity. The CD8+ T cells responding in the presence of agonistic {alpha}CD40 antibody produced large amounts of interleukin 2 and interferon {gamma}, acquired cytolytic function in vivo, emigrated in large numbers to the lung, and responded vigorously to OVA rechallenge. Therefore, DEC-205 provides an efficient receptor-based mechanism for DCs to process proteins for MHC class I presentation in vivo, leading to tolerance in the steady state and immunity after DC maturation.

Key Words: dendritic cells • DEC-205 receptor • tolerance • CD8 T cell • MHC class I


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS