IntroductionThe observation was made several years ago in this laboratory that different strains of mice demonstrated marked differences in their antibody response capacity to staphylococcal nuclease (nuclease). Further investigations showed that the levels of antibody produced to nuclease in mice were under genetic control by genes in the/1" region of the H-2 complex, and thus defined another Ir gene, termed Ir-Nase [16]. The majority of responses previously demonstrated to be under Ir gene control were to synthetic polypeptide antigens in which antigenic determinants presumably occur repeatedly throughout the polypeptide chain. Nuclease, on the other hand, was a natural globular protein with a nonrepeating amino acid sequence, such that each antigenic determinant should occur only once per molecule. Because of this feature, as well as the wealth of structural, chemical and immunochemical information available for nuclease, it was decided that nuclease might provide a valuable model for investigations of the basis of genetic control of immune responses. Studies were therefore initiated to examine the immune response of mice to nuclease at several levels and to develop probes for antigen specific receptors which might be used to study cellular interactions involved in the immune response to nuclease both in vivo and in vitro. This review is intended as an interim progress report on these studies. It is divided into four sections each dealing with one of the major avenues of our current research. The first provides background information on the chemistry and immunochemistry of nuclease; the second deals with progress in defining the genetics of control of the humoral response to nuclease and to fragments of nuclease ; the third concerns development of a T cell proliferative response to nuclease and the consideration Address offprint requests to: