The Atomic Mobility Component of Protein Antigenicity

A full understanding of the cellular immune response requires a detailed knowledge of the structural basis for protein antigenicity at a molecular level that approaches atomic resolution. The development of techniques using anti-peptide antibodies ( 1 , 2) as well as the continued growth of information derived using monoclonal antibodies to whole proteins (3) makes it possible to examine the antigenicity of specific protein sites. As a result, recent studies, using both anti-peptide antibodies corresponding to protein sites and monoclonal antibodies that are directed against proteins of known three-dimensional structure have produced new information concerning the relationship between antigenicity and protein structure. In the simplest sense, antigenic determinants or epitopes of proteins represent those amino acid residues that interact with the binding site of an antibody molecule. It is now apparent that the set of antigenic specificities seen after immunization with the native protein is not representative of the entire potential antigenic repertoire. Yet, certain sequences and residues have been identified as immunodominant sites in that they represent epitopes to which most of the immune response is directed. Although the exact mechanism is unknown, immunodominance has been attributed to either intrinsic structural properties of the antigen or host regvlatory mechanisms including tolerance, immune gene response, and specificity of T-cell help. While it is likely that both intrinsic and regulatory mechanisms