As a medical student and house staff at Stanford University School of Medicine and Stanford University Hospital, I was exposed to research in immunology and systemic lupus erythematosus. As a student and faculty member associated with the late Dr. Henry Kunkel at the Rockefeller University, I was deeply involved in various aspects of human immunological research. During this period, I continued to care for a few patients with SLE and was instrumental in organizing the serum bank in the laboratory. I was primarily responsible for the mapping of the C2 gene (the second complement component) within the MHC. I was involved in the identification of the two chain structures of the HLA-DR molecule and the generation of the homozygous cell line for typing of the HLA-D region. I also developed an interest in the role of MHC as a disease susceptibility gene in autoimmune diseases such as multiple sclerosis (MS), SLE and rheumatoid arthritis. At the Oklahoma Medical Research Foundation (OMRF), I collaborated with Dr. M. Reichlin and Dr. J. Harley to study the linkage of HLA-D region genes to autoantibody production. During the past 15 years, I have adopted NZM2328 as a lupus-nephritis model and have done extensive studies on the mechanisms of autoantibody diversification. We have demonstrated endogenous autoantigens play a crucial role on epitope spreading at the B cell level. This process involved autoreactive T cells to various T cell epitopes within the autoantigen of interest. From these studies, we have gained great insight into the role of crossreactive T cells to autoantigens and conventional environmental antigens in the induction of an autoimmune response to SmD and its peptides.