Idiotypes and Anti-Idiotypes

Idiotypes (Ab1) are the antigenic determinants of immunoglobulin molecules that are located in the variable region of the antibodies. Anti-idiotypic antibodies (Ab2) are directed against the idiotypic determinants. They are classified into Ab2 alpha, which recognize Ab1 framework region antigen; Ab2 beta, which bind the antigen-binding site of the antibody molecule; Ab2 gamma refer to antibodies directed against idiotypes close to, rather than within the antigen-binding site; and Ab3, which are anti-anti-idiotypic antibodies. Under physiologic conditions, each antigenic stimulation leads to the production of idiotypes Ab1 and anti-idiotypes (Ab2 and Ab3) as a network of interacting antibodies; this idiotypic network has a crucial role in the regulation of immune response to external and self-antigens. Manipulation of the idiotypic network can also be implicated in the production of pathogenic autoantibodies and induction of autoimmune diseases. Experimental autoimmune diseases include systemic lupus erythematosus, antiphospholipid syndrome, and others have been induced by immunization of mice with polyclonal human anti-deoxyribonucleic acid (DNA) and anticardiolipin antibodies (aCL). In subjects susceptible to autoimmune diseases, the immune response to particular antigens extends over weeks to months and ends with production of idiotypic antibodies that recognize pathogenic epitopes and eventually with the development of an overt autoimmune disease. Immunologic suppression of pathogenic idiotypes, by manipulation of the idiotypic network with anti-idiotypic antibodies, has a therapeutic implication. This has been achieved by intravenous immunoglobulin (IVIG), a small fraction of anti-idiotypes from IVIG, and by peptides identical to sequences in pathogenic antibodies to DNA.