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Journal of Virology, September 2001, p. 8579-8588, Vol. 75, No. 18
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.18.8579-8588.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Identification of the Immunodominant H-2Kk-Restricted Cytotoxic T-Cell Epitope in the Borna Disease Virus Nucleoprotein

Karin Schamel, Peter Staeheli, and Jürgen Hausmann*

Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, D-79104 Freiburg, Germany

Received 26 February 2001/Accepted 14 June 2001

Borna disease virus (BDV)-induced immunopathology in mice is most prominent in strains carrying the major histocompatibility complex H-2k allele and is mediated by CD8+ T cells that are directed against the viral nucleoprotein p40. We now identified the highly conserved octamer peptide TELEISSI, located between amino acid residues 129 and 136 of BDV p40, as a potent H-2Kk-restricted cytotoxic T-cell (CTL) epitope. When added to the culture medium of L929 target cells, TELEISSI conferred sensitivity to lysis by CTLs isolated from brains of BDV-infected MRL mice with acute neurological disease. Vaccinia virus-mediated expression of a p40 variant with mutations in the two Kk-specific anchor residues of the TELEISSI peptide (p40E130K,I136T) did not sensitize L929 target cells for lysis by BDV-specific CTLs, whereas expression of wild-type p40 did. Furthermore, unlike vaccination with wild-type p40, vaccination of persistently infected symptomless B10.BR mice with p40E130K,I136T did not result in central nervous system inflammation and neurological disease. These results demonstrate that TELEISSI is the immunodominant CTL epitope of BDV p40 in H-2k mice.

* Corresponding author. Mailing address: Department of Virology, University of Freiburg, Hermann-Herder-Str. 11, D-79104 Freiburg, Germany. Phone: 49-761-203-6622. Fax: 49-761-203-6562. E-mail: hausmann{at}ukl.uni-freiburg.de.

Journal of Virology, September 2001, p. 8579-8588, Vol. 75, No. 18
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.18.8579-8588.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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