Antibody Structure and Molecular Immunology

Some sciences are exciting because of their generality and some because of their predictive power. Immunology is particularly exciting, however, because it provokes unusual ideas, some of which are not easily come upon through other fields of study. Indeed, many immunologists believe that for this reason, immunology will have a great impact on other branches of biology and medicine. On an occasion such as this in which a very great honor is being bestowed, I feel all the more privileged to be able to talk about some of the fundamental ideas in immunology and particularly about their relationship to the structure of antibodies. Work on the structure of antibodies has allied immunology to molecular biology in much the same way as previous work on hapten antigens allied immunology to chemistry. This structural work can be considered the first of the projects of molecular immunology, the task of which is to interpret the properties of the immune system in terms of molecular structures. In this lecture, I should like to discuss some of the implications of the structural analysis of antibodies. Rather than review the subject, which has been amply done (1-4), I shall emphasize several ideas that have emerged from the structural approach. Within the context of these ideas, I shall then consider the related but less well explored subject of antibodies on the surfaces of lymphoid cells, and describe some recently developed experimental efforts of my colleagues and myself to understand the molecular mechanisms by which the binding of antigens induces clonal proliferation of these cells. Antibodies occupy a central place in the science of immunology for an obvious reason: they are the protein molecules responsible for the recognition of foreign molecules or antigens. It is, therefore, perhaps not a very penetrating insight to suppose that a study of their structure would be valuable to an understanding of immunity. But what has emerged from that study has resulted in both surprises and conceptual reformulations. These reformulations provided a molecular basis for the selective theories of immunity first expounded by Niels Jerne (5) and MacFarlane Burnet (6) and therefore helped to bring about a virtual revolution of immunological thought. The fundamental idea of these theories is now the central dogma of modern immunology: molecular recognition of antigens occurs by selection among clones of cells already committed to producing the appropriate antibodies, each of different specificity (Figure 1). The results of many studies by