Anti-idiotypes as surrogate antigens: structural considerations

The immune response generates antibodies with combining sites complementary to the antigen. These molecules carry antigenic determinants which together define the idioype (Id) of that antibody. An anti-Id response generates some antibodies which complements the antigen-binding surface of the first population of antibodies, and thus represent, in Jerne's words(1), an 'internal image' of the antigen. In this journal recently, Erlanger(2) discussed the difficulties in accepting this concept caused by the persistent notion of the antibody combining site as a groove or cleft. Here Ivan Roitt and his colleagues return to this discussion and define three distinct sets of structural circumstances in which an anti-Id may substitute for an antigen.