Two major histocompatibility complex class I-restricted epitopes of the Borna disease virus p10 protein identified by cytotoxic T lymphocytes induced by DNA-based immunization.
Borna disease virus (BDV) infection of Lewis rats is the most studied animal model of Borna disease, an often fatal encephalomyelitis. In this experimental model, BDV-specific CD8(+) cytotoxic T lymphocytes (CTLs) play a prominent role in the immunopathogenesis of infection by the noncytolytic, persistent BDV. Of the six open reading frames of BDV, CTLs to BDV X (p10) and the L-polymerase have never been studied. In this study, we used plasmid immunization to investigate the CTL response to BDV X and N. Plasmid-based immunization was a potent CTL inducer in Lewis rats. Anti-X CTLs were primed by a single injection of the p10 cDNA. Two codominant p10 epitopes, M(1)SSDLRLTLL(10) and T(8)LLELVRRL(16), associated with the RT1.A(l) major histocompatibility complex class I molecules of the Lewis rats, were identified. In addition, immunization with a BDV p40-expressing plasmid confirmed the previously reported RT1.A(l)-restricted A(230)SYAQMTTY(238) peptide as the CTL target for BDV N. In contrast to the CTL responses, plasmid vaccination was a poor inducer of an antibody response to p10. Three injections of a recombinant eukaryotic expression plasmid of BDV p10 were needed to generate a weak anti-p10 immunoglobulin M response. However, the antibody response could be optimized by a protein boost after priming with cDNA.
Department of Bioscience, Salem International University, Salem, West Virginia 26426-0500, USA.
Yoshio
Y
Hashimoto
Horng-Shen
HS
Chen
Cynthia
C
Cunningham
Tahir H
TH
Malik
Patrick K
PK
Lai
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001890:Borna Disease / Q000276:immunology / Q000517:prevention & control; D001891:Borna disease virus / Q000276:immunology*; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D007114:Immunization; D008969:Molecular Sequence Data; D010957:Plasmids; D051381:Rats; D011917:Rats, Inbred Lew; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology
D000914:Antibodies, Viral; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D019444:Vaccines, DNA; D014764:Viral Proteins; D014765:Viral Vaccines; C119397:p10 protein, Borna disease virus; C077347:p40 protein, Borna disease virus