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International Immunology Advance Access published online on March 18, 2005
International Immunology, doi:10.1093/intimm/dxh232
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© The Japanese Society for Immunology. 2005. All rights reserved. For permissions, please e-mail: journals.permissions@oupjournals.org
Received October 27, 2004
Accepted February 4, 2005

Article

Highly efficient antigen targeting to M-DC8+ dendritic cells via Fc{gamma}RIII/CD16-specific antibody conjugates

Ines Mende 1, Patrick Hoffmann 1, Andreas Wolf 1, Ralf Lutterbüse 1, Eugen Kopp 2, Patrick A. Baeuerle 1, Annegret de Baey 3, and Peter Kufer 4*

1 Micromet AG, Staffelseestrasse 2, 81477 Munich, Germany
2 Institute for Immunology, Ludwig-Maximilians-University, Goethestrasse 31, 80336 Munich, Germany
3 Techno Venture Management, Maximilianstrasse 35C, 80539 Munich, Germany
4 Micromet AG, Staffelseestrasse 2, 81477 Munich, Germany; Institute for Immunology, Ludwig-Maximilians-University, Goethestrasse 31, 80336 Munich, Germany

* To whom correspondence should be addressed.
Peter Kufer, E-mail: peter.kufer{at}micromet.de


  Abstract

Conjugates of peptide antigens with antibodies specifically recognizing surface molecules on dendritic cells (DC) represent an attractive approach to target antigens to antigen-presenting cells (APC) for the induction of specific T cell responses. The present study evaluates the potential of M-DC8+ DC, a sub-population of professional APC in the blood, for an antibody-based vaccination strategy. We prepared, by chemical cross-linking, conjugates of peptide model antigens with antibodies directed against different cell surface molecules of DC. Antigen-peptide conjugates using an anti-CD16 (Fc{gamma}RIII) antibody were most potent in inducing in vitro activation of a specific CD4+ T cell response. They were at least 300 times more efficient than two other antibody-antigen conjugates and ~500 times more efficient than unconjugated antigen peptides. Our data demonstrate that specific antigen targeting via CD16 on M-DC8+ DC is a promising vaccination approach for the efficient induction of specific CD4+ T cell responses ex vivo, and perhaps in vivo.

Keywords: antibodies; antigen presentation; dendritic cells; Fc receptors; vaccination.
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