IN-VIVO ANTAGONISM OF A T-CELL RESPONSE BY AN ENDOGENOUSLY EXPRESSED LIGAND

3.L2 T cell receptor transgenic T cells are activated by the 64-76 pep tide of the mouse hemoglobin d beta chain [Hb(64-76)], and their respo nse is antagonized by the position 72 alanine substitution of this pep tide (A72). To test the effect of this altered peptide ligand (APL) on 3.L2 T cell function in vivo, a transgene expressing A72 in major his tocompatibility complex II positive cells (A72tg) has been introduced into mice. We demonstrate that 3.L2 T cells, when transferred to A72tg (+) mice show a dramatically reduced proliferative response to Rb(64-7 6). Identical decreased responses were observed using T cells that dev eloped in either A72tg(+) or A72tg(-) hosts. This affect was not attri butable to diminished precursor frequency, anergy, or competition for binding to I-E-k molecules. These results unequivocally demonstrate in vivo antagonism by an endogenous APL and characterize a class of self -peptides that, although inefficient in causing deletion in the thymus , effectively modulate T cell responses in the periphery.