The immune system specifically defends the body against threats to its integrity. It is a complex system involving both humor and cell-mediated reactions. As in any complex system, many, if not most, of the cellular elements are involved in self-regulation. The immune system is very well adapted to recognize foreign cells and molecules. In order to accomplish this, however, the system must have the ability to distinguish self from non-self. The major regulatory cells are helper (Th) and suppressor (Ts) thymus-derived lymphocytes. Self-recognition is complicated by the dual nature of the receptor(s) that T cells bear. T cells must recognize both antigen and major histocompatibility complex (MHC, H-2 in the mouse) molecules. Many of the genes encoding the Th antigen-receptor have been recently sequences. Antigen-specific I-J molecules are expressed by Ts and their soluble products, TsF (Ts factors). Our preliminary data show that I-J molecules recognize MHC class II (e.g. I-E) structures. This makes I-J molecules likely candidates for MHC class II self-recognition structures. We propose to direct the activities of our laboratory to the characterization of I-E recognition by I-J, the recognition of other MHC class II structures by I-J; and finally, characterize the cellular targets of I-J molecules. Our proposal tests the hypothesis that I-J molecules function, at least as a class of self-recognition structures.