Enhancement of EAE and induction of autoantibodies to T-cell epitopes in mice infected with a recombinant vaccinia virus encoding myelin proteolipid protein.
SJL/J mice were infected with a recombinant vaccinia virus encoding myelin proteolipid protein (PLP) (VVplp). Antibody responses to whole PLP and to encephalitogenic peptides, p139-151, p178-191 or p104-117 were measured after vaccination and following challenge with these three PLP peptides. Competitive ELISAs showed that antibodies to p139-151 and p178-191 represented the majority of antibodies in the anti-PLP antibody response following VVplp vaccination, since the antibodies to intact PLP could be inhibited 56, 35 and 1%, respectively, by p139-151, p178-191 and p104-117. After peptide challenge, epitope specific anti-peptide antibodies were enhanced. These anti-peptide antibodies also reacted with the intact PLP molecule. Interestingly, the mean titer of anti-p139-151 antibody in p139-151 challenged mice was significantly higher than that observed for anti-p178-191 in p178-191 and for anti-p104-117 in p104-117 challenged mice. Following peptide challenge, the anti-PLP IgG response shifted from an IgG1 to an IgG2a and 2b phenotype. In these mice, both the clinical disease and histological pattern of experimental allergic encephalomyelitis (EAE) were enhanced. The enhancement was most pronounced in the pathologic scores in the p139-151 challenged group followed by p104-117 challenged mice. Thus, humoral immune responses to PLP encephalitogenic peptides can be generated with virus encoding a self central nervous system (CNS) protein.
Wang
L Y
LY
Department of Neurology, University of Utah School of Medicine, Salt Lake City 84132, USA.
Fujinami
R S
RS
D000818:Animals; D000917:Antibody Formation; D001323:Autoantibodies / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D000939:Epitopes; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D018991:Myelin Proteolipid Protein / Q000235:genetics*; D010446:Peptide Fragments / Q000276:immunology; D011995:Recombination, Genetic; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination; D014615:Vaccinia / Q000276:immunology* / Q000821:virology; D014616:Vaccinia virus / Q000235:genetics*
D001323:Autoantibodies; D000939:Epitopes; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments