Role of complementary proteins in autoimmunity: an old idea re-emerges with new twists

It has been suggested that complementary proteins are involved in autoimmunity through a network involving idiotype–anti-idiotype reactions termed ‘autoantigen complementarity’. We propose that complementary proteins, which occur naturally or result from cellular dysfunction, might be more common than recognized currently. This implies that the role of complementary proteins in autoimmunity merits increasing investigation. The concept of complementary proteins is reviewed here and, also, new ideas are presented that underscore the role of open-reading frames in frame −1 of recognized genes in the production of complementary proteins (frame −1 is the reverse complement sequence of a gene that uses the antisense of the codons of frame +1). Furthermore, a novel role for palindromic sequences in autoimmunity and a new model explaining how abzymes and autoantigen complementarity might be related are proposed.