CANONICAL STRUCTURE REPERTOIRE OF THE ANTIGEN-BINDING SITE OF IMMUNOGLOBULINS SUGGESTS STRONG GEOMETRICAL RESTRICTIONS ASSOCIATED TO THE MECHANISM OF IMMUNE RECOGNITION

Is the structural repertoire of immunoglobulins free to adopt an almos t infinite number of conformations:to build the diversity of the immun e response or does it take advantage of only a few conformations? In t his paper we study this question by applying the canonical structure m odel to characterize the structural repertoire of immunoglobulins. The results found, indicate that only ten combinations out of the 300 pos sible different canonical structure classes (combinations of canonical structures), make up 87% of 381 sequences analyzed. This suggests tha t the structural repertoire of immunoglobulins is restricted to the pr eferential use of a small number of canonical structure classes. The p ossible functional significance of these results was studied by analyz ing the correspondence between the observed canonical structural reper toire implicit in Ig sequences and the types of antigens recognized. T wo different sets of canonical structure classes were distinguished: o ne with preference for some specific types of antigens like proteins, polysaccharides or haptens, and the other with multi-specific binding capabilities. Analysis of antibodies of known three-dimensional struct ure shows that for two specific classes, the canonical conformations o f H2 and L1 determine the geometrical characteristics of the antigen-b inding site, while at least in one multi-specific class, the changes i n the general geometry of the antigen-binding site are produced by dif ferent conformations of H3. Implications of these results for the mole cular by immunoglobulins are discussed. (C) 1995 Academic Press Limite d