Two human IgM myeloma proteins with unusual specificities for streptococcal carbohydrate-associated epitopes.
Five hundred and fifty human sera from patients with IgM myeloma or Waldenström's macroglobulinaemia were screened by a solid-phase enzyme-linked immunoassay for binding to the carbohydrate of group A streptococci (A-CHO). Two of them (AC8 and AC179) contained immunoglobulin, which bound specifically to A-CHO even at serum dilutions of 1:10(7). Using synthetic oligosaccharides coupled to protein for inhibition studies, the fine specificities of AC8 and AC179 were determined. AC179 is directed to alpha-linked rhamnose oligosaccharides. AC8 appears to be specific for N-acetyl-D-glucosamine (GlcNAc) side chains beta(1----2)-linked to rhamnose, whereas GlcNAc side chains in A-CHO are reported to be beta(1----3)-linked to the rhamnose backbone. Naturally occurring anti-A-CHO antibodies consist mainly of low-affinity antibodies to such beta(1----3)-linked GlcNAc. In contrast, both myeloma antibodies show more than 10 times higher relative affinities to A-CHO than antibodies prepared from normal human serum (anti-GlcNAc and anti-A-CHO, respectively) by selection for high affinity in the elution procedure. AC179 induced complement activation in the presence of A-CHO.
Emmrich
F
F
Bundle
D
D
van der Zee
J
J
Out
T
T
Zenke
G
G
Eichmann
K
K
D000117:Acetylglucosamine / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000502:physiology; D000942:Antigens, Bacterial / Q000276:immunology; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D003167:Complement Activation; D003172:Complement C1 / Q000378:metabolism; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism*; D009194:Myeloma Proteins / Q000378:metabolism*; D011135:Polysaccharides, Bacterial / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D013291:Streptococcus / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D003172:Complement C1; D000939:Epitopes; D007075:Immunoglobulin M; D009194:Myeloma Proteins; D011135:Polysaccharides, Bacterial; C036112:streptococcal polysaccharide group A; D000117:Acetylglucosamine