Alterations in major histocompatibility complex association of myocarditis induced by coxsackievirus B3 mutants selected with monoclonal antibodies to group A streptococci.
Three monoclonal antibodies (mAbs), 49.8.9, 36.2.2, and 54.2.8, made to the group A streptococcus M5 serotype identify crossreactive epitopes in cardiac tissues and also neutralize a highly myocarditic variant of coxsackievirus B3 (H3). Mutants of H3 were selected with these mAbs and evaluated for pathogenicity compared with the wild-type virus. H3 and the mutant variants selected with mAbs 36.2.2 (H3-36) and 54.2.8 (H3-54) induced severe myocarditis in DBA/2 (H-2d) and A/J (H-2a) male mice, whereas CBA (H-2k) mice were disease resistant. The virus variant isolated with mAb 49.8.9 (H3-49) was strikingly different and caused disease in CBA and A/J mice but not in DBA/2 animals, suggesting that the major histocompatibility complex association of the disease had been altered. This hypothesis was confirmed by using B10 congenic mice. In addition, T lymphocytes from the H3 and H3-49 virus-infected mice responded to distinctly different peptides in the streptococcal M protein, suggesting that certain epitopes of infectious agents which are shared with host tissues may be critical in determining disease susceptibility in genetically distinct individuals.
Huber
S A
SA
Department of Pathology, University of Vermont, Burlington 05405.
Moraska
A
A
Cunningham
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology*; D002352:Carrier Proteins; D029822:Enterovirus B, Human / Q000276:immunology / Q000472:pathogenicity*; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009205:Myocarditis / Q000276:immunology* / Q000382:microbiology; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D013297:Streptococcus pyogenes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D010455:Peptides; C014689:streptococcal M protein