Mimetics of a T Cell Epitope Based on Poly-N-acylated
Amine Backbone Structures Induce T Cells in Vitro and
in Vivo*
Sascha
Hin
,
Alberto
Bianco§¶,
Claus
Zabel
,
Günther
Jung§, and
Peter
Walden
**
From the
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.