Idiotypes and Antiidiotypic Antibodies in Health and Disease

Abstract

The diversity and effectiveness of the humoral immune response depends upon the huge number of different antibodies which a single individual can produce, estimated to be at least 100 million. Although some variation in the function of antibodies depends upon their class (isotype) the greatest part of antibodies' differences among themselves is due to the variable regions of the heavy and light chains, where the antibody combines with its antigen. These particular variations in immunoglobulin structure were detected over a quarter of a century ago by the production of a second generation of antibodies against the antigenic determinants of the polypeptides of the variable region of the first generation of antibodies injected into experimental animals [1-3]. The antigenic structure of the immunoglobulin molecule so defined became known as its 'idiotype', and the antibodies directed against the idiotypes are known as 'antiidiotypic antibodies' or 'antiidiotypes'. The individual antigenic determinants which together make up the idiotype are known as 'idiotopes' (Fig. 1). A single immunoglobulin molecule contains many idiotopes and can therefore give rise to a large number of antiidiotypic antibodies, distinct from each other, but all capable of reacting with the original immunoglobulin. As the antiidiotypes are directed against the Fab region of the first antibody, they are distinct from rheumatoid factors, i.e. antibodies directed against the constant Fc portion. Antiidiotypes may be of two sorts raised experimentally in the same or a foreign species, or arising in the host itself, i.e. an auto-antiidiotypic antibody. In many articles and papers, the prefix 'auto' is not used in the description of these autoantibodies, as it is usually clear from the context that autoantibodies are being described. The recognition of idiotypes and the production in normal and diseased subjects of autoantiidiotypic antibodies has led to concepts which are important in understanding the function of the immune system and, more recently, attempts to use them therapeutically.