The autologous (or syngeneic) mixed lymphocyte reaction (AMLR) in mice is a measure of proliferation of Ly 1+23- T cells which occurs when they are cultured with non-T cells from the same animal. The recognition event is mediated by cell surface antigens encoded in the I region of the major histocompatibility complex. This recognition event is associated with the development of suppressor cells which affect proliferative and cytotosic responses of fresh T cells in mixed lymphocyte culture and also with helper cells which cause differentiation of cytotoxic T cells recognizing hapten-modified self cell surface determinants. The helper cells act by elaboration of a factor which, on preliminary study, appears to be interleukin-2 (IL-2). The AMLR is present in young mice of the autoimmune strain, NZB, but is with failure to generate cytotoxic cells recognizing modified self. The proposed studies will examine in greater detail the range of helper and suppressor functions associated with the AMLR, determine the requirements for generating cells with these functions and their mechanism of action (i.e., soluble mediator production and their induction by feedback circuits). The ontogeny of the AMLR, the relationship of other T cell subsets to AMLR responder T cells, and changes in AMLR relative to age will also be examined. Studies in which the receptor system through with AMLR occurs will employ anti-idiotype antisera to hybridoma anti-IA antibodies and immunizations of mice with AMLR-induced blasts. Finally, in the NZB mouse model, the extent of AMLR-related functional deficiencies will be determined along with investigation, both in vitro and in vivo, of the reversibility of any identified lesions. These latter studies will allow some conclusions regarding the potential for any therapeutic applications in humans of our findings.