The availability of structurally well-defined synthetic antigens permitted the elucidation of many aspects of the molecular basis of antigenicity as well as of other immunological phenomena. Due to recent progress in cellular immunology, it is now possible to reach a more detailed understanding of the various components underlying the nature of antigenicity. The present proposal is devoted mainly to two topics of paramount importance for a better grasp of immunological phenomena: genetic control of immune response, and autoimmunity. Significant progress in elucidating the mechanisms responsible for generating genetic variations in the immune system was made only by studying the genetic control of responses to immunogens which contain a restricted number of defined antigenic determinants (synthetic antigens). One of the objectives of the proposed research is to continue to analyse the genetic control of immune response at the molecular and cellular levels, using new synthetic polypeptides and synthetic antigens better defined structurally, to elucidate the mechanism(s) by which immune response genes are operating, to establish the role of the different cell types in the immune response as a function of the antigen structure and the genetic constitution of the animal, and to determine whether low responsiveness can be attributed to a particular class of antibody or of antibody-producing cells. In recent years we have become interested in the genetic regulation and cellular basis of the immune response to collagen and nucleic acids. Both these types of molecules have unique structural features on the one hand, and they are known to be involved in some immunological disorders, e.g., autoimmune diseases, on the other hand. Collagen-like synthetic models and other synthetic conjugates are also being applied in these studies.