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.