Relationship between naturally occurring human antibodies to casein and autologous antiidiotypic antibodies: implications for the network theory.

Previous studies on human autologous antiidiotypes have been based largely upon analyses of autoimmune disease. We have previously described polyclonal, naturally occurring human autoantibodies directed against antibodies with specificity toward bovine casein in the sera of IgA-deficient humans. In order to define this system more exactly we have not produced two murine monoclonal antibodies directed against bovine milk kappa-casein to use as clonal tools to identify specific antiidiotypes in these human sera. Kappa-casein is an important part of the casein micelle in milk and cheese; in addition to being an important immunogen for man, kappa-casein is known to have conserved amino acid sequence and two antigenic epitopes. Data presented here show that the serum of up to 74% of IgA-deficient and 10% of normal humans have specific autologous antiidiotypes in their serum which bind to monoclonal antibodies directed to bovine kappa-casein. These human antibodies [intact or F(ab)'2] can be blocked from binding to the monoclonal anti-kappa-caseins by pure bovine kappa-casein or the kappa-casein peptide fragment. In contrast to previous studies in autoimmune disease, serum levels of the autoantiidiotypes were directly proportional to the level of IgG antibody to bovine kappa-casein. These observations suggest that continual exposure to a ubiquitous dietary antigen may produce an antigen driven system in which stimulation of both Ab1 and Ab2 occurs in concert.