The key elements of antigen-binding immunoglobulin (Ig) variable regio
ns are primarily encoded by diversity (D-H) genes. Although D-H genes
can be used in all three reading frames, the majority of peripheral Ig
molecules carry a D-H element in a single reading frame. Here, Frank
Raaphorst, C. Raman, Barry Nall and Judy Teale discuss the particular
demands imposed by the structure of the antigen-binding site, which de
termine the choice of reading frame.