Identification of the immunodominant H-2K(k)-restricted cytotoxic T-cell epitope in the Borna disease virus nucleoprotein

Borna disease virus (BDV)-induced immunopathology in mice is most prominent in strains carrying the major histocompatibility complex H-2k allele and i s mediated by CD8(+) T cells that are directed against the viral nucleoprot ein p40. We now identified the highly conserved octamer peptide TELEISSI, l ocated between amino acid residues 129 and 136 of BDV p40, as a potent H-2K (k)-restricted cytotoxic T-cell (CTL) epitope. When added to the culture me dium of L929 target cells, TELEISSI conferred sensitivity to lysis by CTLs isolated from brains of BDV-infected MRL mice with acute neurological disea se. Vaccinia virus-mediated expression of a p40 variant with mutations in t he two K-k-specific anchor residues of the TELEISSI peptide (p40(E130K,I136 T)) did not sensitize L929 target cells for lysis by BDV-specific CTLs, whe reas expression of wild-type p40 did. Furthermore, unlike vaccination with wild-type p40, vaccination of persistently infected symptomless B10.BR mice with p40(E130K,I136T) did not result in central nervous system inflammatio n and neurological disease. These results demonstrate that TELEISSI is the immunodominant CTL epitope of BDV p40 in H-2k mice.