IDIOTYPES - STRUCTURE AND IMMUNOGENICITY

Idiotopes are markers on the variable domains of antigen-specific immunological receptors recognized by anti-idiotypic antibodies or T cells. Therefore, a given antibody or T cell receptor can be identified on the basis of a characteristic idiotypic pattern. The structural correlates for idiotopes on antibodies have been studied by competitive binding assays, electron microscopy, site-directed mutagenesis, and X-ray crystallography. Immunoglobulin idiotopes, recognized by anti-idiotypic antibodies, can involve amino acid residues from several hypervariable or framework regions and from either or both of the heavy and light chain variable domains. Recent studies suggest that it may be possible to exploit structural knowledge of idiotopes and anti-idiotopes for the design of new ligands for immunological or other cell surface receptors. In one instance, it has been possible to use the inferred structural features of an anti-idiotope, which mimics a viral protein, to design a small organic molecule with functional properties approximating those of the antigen and the native anti-idiotope. An alternative strategy being explored for creating new vaccines or therapeutic agents involves engineering an amino acid sequence, corresponding to a segment of a selected nominal antigen, into an immunoglobulin variable domain.