The study of MHC restriction of T cell specificity and more particularly the relationship of this phenomenon to Ir gene function, has been a major concern of our laboratory. This project addresses three aspects of the specificity of T lymphocytes restricted to react with antigen and self Ia molecules. 1. The nature of Ia-antigen interactions, and the specificity of T cell receptors for self Ia. 2. The control of IL-1 production at the level of the antigen presenting cells and the role of Ia molecules in this process. 3. The selection of a differentiating T cell population in the thymus restricted to react specifically with self Ia molecules.