This program project has always been concerned with the nature of the surface of virus infected and/or transformed cells and the mechanisms of immunologic attack against these altered surfaces. For instance it was under the auspices of this program project that the chemical nature and relationship to the cell surface of the retroviral glycoprotein, gp70 and its anchor protein 15E were described. We continue this theme in this new grant proposal, and continue our use of the most modern concepts and technologies available for the study of the process by which the immune system attacks viruses or the transformed cell surface. Modern cell biology and immunochemistry have made enormous gains during the years we have enjoyed support of this program project. As detailed below, we feel that our research efforts have contributed to the success of these disciplines and herein present our renewal application which, if funded, should allow us to carry out research at the forefront of immunology and cell biology as it pertains to virus infection and neoplasia. In this program project we have brought together cell biologists, immunologists and chemists to take a concerted approach to this problem. We are very excited about this program project because we feel that we are in a position to use all of the tools of modern cell biology and chemistry to make advances every bit as important as some of the outstanding milestones which have occurred over the last ten to twenty years. For example, it may be during the tenure of this program project that we see the first structure of an antibody molecule in solution by NMR or the birth of a technology which uses the power of molecular genetics to replace the more cumbersome hybridoma technology to access the antibody repertoire. We almost certainly will understand much more of the cell biology of immune induction and cellular transformation and will likely learn how to make better anti-viral and anti-tumor reagents.