T lymphocyte responses in CVB3-induced murine myocarditis.
Three monoclonal antibodies (mAB) to group A streptococcus M5 serotype (mAB 36.2.2, 49.8.9 and 54.2.8) cross-reactivity bind to various heart antigens (including myosin, tropomyosin and vimentin) and neutralize a myocarditic variant of coxsackievirus B-3 (Nancy) (CVB3). The existence of shared antigenic epitopes between the two distinct infectious agents and the heart implies that antigenic mimicry may form the foundation of the autoimmune response. Plaque purified variants of CVB3 were isolated with these streptococcal mAB. The wild-type virus (H3) and the virus variants made with mABs 36.2.2 (H3-36) and 54.2.8 (H3-54) caused significant myocarditis in Balb/c (H-2d) mice, but not in CBA (H-2k) animals. The virus variant made with mAB 49.8.9 (H3-49) caused myocarditis in CBA, but not in Balb/c mice. No significant differences in virus concentrations in the heart were detected with any of the virus variants. Cytolytic activity of mesenteric lymph node cells generally correlated to the severity of myocarditis in the infected animals. Using overlapping synthetic peptides of the CVB3 VP1 protein, mAB 49.8.9 was shown to bind preferentially peptides 6, 8, 11, and 12. T lymphocytes from H3 infected mice proliferated to VP1 peptides 1, 3, 9, 13, 14, and 21. To determine whether immunity to specific peptides could affect CVB3 pathogenicity, Balb/c mice were immunized with VP1 peptides 1, 3, 6, 13, 14 and 21 in complete Freund's adjuvant (CFA) then infected with 5 x 10(4) PFU CVB3 14 days later. Pre-immunization of animals with (a) peptide 1 resulted in a significant decrease in virus titers in the heart, (b) peptides 3, 13 and 21 increased animal mortality and lymphocyte mediated cytotoxicity to uninfected cardiocyte targets, and (c) peptides 3 and 21 resulted in significant increases in myocarditis compared to animals given virus without pre-immunization.
Huber
S
S
Department of Pathology, University of Vermont, Burlington 05405.
Polgar
J
J
Moraska
A
A
Cunningham
M
M
Schwimmbeck
P
P
Schultheiss
P
P
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D015551:Autoimmunity / Q000276:immunology*; D003384:Coxsackievirus Infections / Q000276:immunology*; D003429:Cross Reactions; D029822:Enterovirus B, Human / Q000276:immunology* / Q000472:pathogenicity; D000939:Epitopes / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D009205:Myocarditis / Q000276:immunology* / Q000382:microbiology; D013297:Streptococcus pyogenes; D013601:T-Lymphocytes / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D014764:Viral Proteins