Antigenicity and Immunogenicity

ANTIGENICITY AND IMMUNOGENICITY

Antigenicity is defined as the property of a substance (antigen) that allows it to react with the products of a specific immune response (antibody or T-cell receptor). On the other hand, immunogenicity is defined as the property of a substance (immunogen) that en-dows it with the capacity to provoke a specific immune response. From these definitions it follows that all immunogens are antigens; the reverse, however, is not true, as dis-cussed later.

B-cell immunogens are usually complex, large molecules that are able to interact with B-cell surface receptors (membrane immunoglobulins) and deliver the initial activat-ing signal leading to clonal expansion and differentiation of antibody-producing cells. T-cell immunogens can be best defined as compounds that can be processed by antigen-pre-senting cells into short polypeptide chains that combine with MHC molecules; the peptide-MHC complexes are able to interact with specific T-cell receptors and deliver ac-tivating signal to the T cells carrying such receptors.

Landsteiner, Pauling, and others discovered in the 1930s and 1940s that small aro-matic groups, such as amino-benzene sulfonate, amino-benzene arsenate, and amino-ben-zene carboxylate, unable to induce antibody responses by themselves, would elicit antibody formation when chemically coupled to immunogenic proteins. The injection of these com-plexes into laboratory animals resulted in the production of antibodies specific for the dif-ferent aromatic groups. The aromatic groups were designated as “haptens” and the im-munogenic proteins as “carriers.” The immune response induced by a hapten-carrier conjugate included antibodies able to recognize the hapten and the carrier as separate enti-ties. The hapten-specific antibodies are also able to react with soluble hapten molecules, free of carrier protein. Thus, a hapten is an antigen, but not an immunogen. In practical terms, it must be noted that the designations of antigen and immunogen are often used in-terchangeably

Experiments comparing the specificity of hapten-specific antibodies induced with isomers of aromatic groups were critical for the definition of antibody specificity . Experiments comparing the effects of different hapten-carrier combinations or preimmunization with carrier proteins on hapten-specific responses helped to define T-B lymphocyte cooperation. Later, the principles established with hapten-carrier conjugates were expanded to the induction of immune responses di-rected against many small molecular weight compounds and even poorly immunogenic polysaccharides, all of which may induce strong responses after conjugation to an im-munogenic carrier protein. This knowledge helped explain the pathogenesis of some hy-persensitivity disorders and was the basis for the development of improved immunization protocols .