Experimental autoimmune myasthenia gravis (EAMG) can be induced in C57BL/6 (B6) mice by immunization with Torpedo californica acetylcholine receptor (tAChR). We had previously shown that pretreatment with a monomethoxypolyethylene glycol (mPEG) conjugate of myasthenogenic tAChR alpha-chain peptide alpha125-148 (mPEG-peptide) suppressed EAMG. In order to understand the mechanism involving T cells in the induction of this suppression, we have studied, in the present work, the in vitro responses of T cells from mPEG-peptide treated B6 mice after an initial tAChR injection to determine the early effect of mPEG-peptide treatment on these responses. Treatment with mPEG-peptide reduced the T cell responses to tAChR and several tAChR alpha-chain peptides. To further investigate the T cell helper function in vivo, we transferred T cells from B6 mice that received either mPEG-peptide or control PBS followed by two tAChR injections to non-immune B6 mice. T cell transfer from mPEG-peptide pretreated mice down regulated, in recipient mice, Ab induction (after cell transfer) and Ab production (after two tAChR injections) toward alpha-chain peptides. Treatment of B6 mice with mPEG-peptide did not alter the ability of their APC to present peptide alpha146-162 to peptide-specific B6 T cells. The results indicate that suppression of EAMG by treatment with mPEG-peptide is due to T cell involvement and not to a defect in APC function.