The Oklahoma Medical Research Foundation (OMRF) herein proposes a site for a Center for Biomedical Research Excellence (COBRE) on "Molecular Mechanisms and Genetics of Autoimmunity." Research programs in immunology and rheumatic diseases were initiated over 20 years ago at the OMRF and have been steadily growing since. The faculty is responsible for a number of seminal discoveries and has made this an area of research excellence at the OMRF upon which to build this COBRE. We propose four Junior Investigators who have promising futures for biomedical research productivity in the genetics and molecular mechanisms of autoimmunity. Indeed, their projects should have an important impact upon our understanding of important autoimmune disease problems. These Junior Investigators are supported by eight exceptional Mentors, who will provide the guidance and advocacy so important for launching the successful careers of independent scientists. The projects proposed by the Junior Investigators will also be facilitated by a Nucleic Acid Analysis Core and a Data Analysis Core, both of which are directed by very experienced and knowledgeable staff scientists. Indeed, these cores will help efficiently and economically apply the most sophisticated technologies and methods to the problems being addressed in the projects performed by the Junior Investigators. Additional COBRE Junior Investigators will be recruited to this center making this a transitional mechanism for the development of many independent investigators, thereby sustaining the level of excellence now achieved in research into autoimmunity in Oklahoma. The synergies, collaborations, and directed effort of the COBRE will provide a much deeper level of understanding to human autoimmune diseases and will foster the independent career development of a strong group of Junior Investigators.