Cytotoxic and viral neutralizing antibodies crossreact with streptococcal M protein, enteroviruses, and human cardiac myosin.
The development of autoimmunity in certain instances is related to infectious agents. In this report, cytotoxic monoclonal antibodies (mAbs) that recognize epitopes on both enteroviruses and the bacterium Streptococcus pyogenes are described. Murine anti-streptococcal mAbs that were crossreactive with streptococcal M protein, human cardiac myosin, and other alpha-helical coiled-coil molecules were found to neutralize coxsackieviruses B3 and B4 or poliovirus type 1. The viral-neutralizing anti-streptococcal mAbs were also cytotoxic for heart and fibroblast cell lines and reacted with viral capsid proteins on a Western immunoblot. Alignment of amino acid sequences shared between streptococcal M protein, coxsackie-virus B3 capsid protein VP1, and myosin revealed 40% identity in a 14- to 15-amino acid overlap. Synthetic peptides containing these sequences blocked mAb reactivity with streptococcal M protein. The data show that antibodies against alpha-helical structures of bacterial and viral antigens can lead to cytotoxic reactions and may be one mechanism to explain the origin of autoimmune heart disease.
Cunningham
M W
MW
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City 73190.
Antone
S M
SM
Gulizia
J M
JM
McManus
B M
BM
Fischetti
V A
VA
Gauntt
C J
CJ
D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology*; D001667:Binding, Competitive; D002352:Carrier Proteins; D003429:Cross Reactions; D004770:Enterovirus / Q000737:chemistry / Q000276:immunology*; D029822:Enterovirus B, Human / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D009218:Myosins / Q000737:chemistry / Q000276:immunology*; D009500:Neutralization Tests; D010455:Peptides / Q000276:immunology; D017955:Poliovirus / Q000276:immunology; D016415:Sequence Alignment; D013291:Streptococcus / Q000276:immunology*
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D010455:Peptides; C014689:streptococcal M protein; D009218:Myosins