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Originally published In Press as doi:10.1074/jbc.M107552200 on October 12, 2001

J. Biol. Chem., Vol. 276, Issue 52, 48790-48796, December 28, 2001
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Mimetics of a T Cell Epitope Based on Poly-N-acylated Amine Backbone Structures Induce T Cells in Vitro and in Vivo*

Sascha HinDagger , Alberto Bianco§, Claus ZabelDagger ||, Günther Jung§, and Peter WaldenDagger **

From the Dagger  Department of Dermatology and Allergy, Charité, Humboldt University, D-10089 Berlin, Germany and the § Institute of Organic Chemistry, University of Tübingen, D-72076 Tübingen, Germany

Peptidomimetics of the major histocompatibility complex (MHC) class I-restricted ovalbumin-derived T cell epitope SIINFEKL were generated by replacing parts of the peptide backbone by a poly-N-acylated amine (PAA) backbone with aromatic, heteroaromatic, and pseudoaromatic side chains that branch off of the main chain at the amine nitrogen. The structure of the PAAs was designed to position this side chain in the central epitope anchor pocket of the MHC molecule. A number of biologically active PAAs were found that induced cytolysis by the mouse cytotoxic T cell clone 4G3. Competition experiments with independent peptides that are known to bind to the restricting MHC molecule H-2Kb suggest that the PAAs are bound by the MHC molecules at the same site as conventional peptide epitopes. The PAAs were active also in vivo and induced primary cytotoxic T cell responses in mice.


* This work was supported in part by grants from the Deutsche Forschungsgemeinschaft (STE 366/7-4 TP1 and SFB 510, Projects C6 and D4) and the Volkswagen Foundation (I/75 325).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Recipient of a fellowship from the Alexander von Humboldt Foundation. Present address: Institut de Biologie Moléculaire et Cellulaire, Immunologie et Chimie Thérapeutiques, 67084 Strasbourg, France.

|| Present address: Institute for Human Genetics, Charité, Humboldt University, D-10089, Berlin, Germany.

** To whom correspondence should be addressed: Charité, Humboldt University Medical School, Dept. of Dermatology and Allergy, Schumannstr. 20/21, D-10117 Berlin, Germany. Tel.: 49-30-450-518031; Fax: 49-30-450-518932; E-mail: peter.walden@charite.de.


Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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