The objectives of this project are to determine the structure and function of the T-cell immune recptor for insulin and to ascertain how its modulation affects antigen specific T-cell activation. These objectives will be accomplished by using established T-cell clones and newly generated T-cell hybridomas reactive with bovine insulin to prepare antibodies that specifically recognize the T-cell immune receptor. These anti-receptor reagents will then be used to invessigate and modulate the biochemical and physiological events which accompany antigen-specific activation of T cells and culminate in final T-cell effector function. The biochemical and functional characterization of the T-cell receptor and the intracellular events it modulates will be critical to our understanding of the factors controlling the antigen-specific response of this immunoregulatory cell. Aberrant regulation of the immune system has been implicated in the etiology of Type I diabetes mellitus and such therapeutic problems as insulin """"""""allergy"""""""" and the development of insulin antibodies. Delineation of the mechanism and consequences of immune T-cell recognition of insulin will allow strategies for specific immunotherapy in diabetes.
