3-DIMENSIONAL STRUCTURE OF A HETEROCLITIC ANTIGEN-ANTIBODY CROSS-REACTION COMPLEX

Although antibodies are highly specific, cross-reactions are frequentl y observed. To understand the molecular basis of this phenomenon, we s tudied the anti-hen egg lysozyme (HEL) monoclonal antibody (mAb) D11.1 5, which cross-reacts with several avian lysozymes, in some cases with a higher affinity (heteroclitic binding) than for HEL. We have determ ined the crystal structure of the Fv fragment of D11.15 complexed with pheasant egg lysozyme (PHL). In addition, we have determined the stru cture of PHL, Guinea fowl egg lysozyme, and Japanese quail egg lysozym e. Differences in the affinity of D11.15 for the lysozymes appear to r esult from sequence substitutions in these antigens at the interface w ith the antibody. More generally, cross-reactivity is seen to require a stereochemically permissive environment for the variant antigen resi dues at the antibody-antigen interface.