FAILURE OF PRESENTED, NONDOMINANT SELF EPITOPE TO INDUCE TOLERANCE - IMPLICATIONS FOR AUTOIMMUNE-DISEASES

It has been observed that a hierarchy exists among epitopes such that fewer epitopes are actually involved in the induction of T cell respon se and tolerance than there are epitopes available in a given antigen. Some epitopes which are ''cryptic'' for immune activity within the pr otein, are nevetherless able to elicit a response if administered alon e and can also be used to by-pass tolerance. We report that tolerance to a self protein shows the same phenomenon seen for non self proteins . In fact, we elicit a proliferative response toward a predicted minor cryptic epitope, to which animals are clearly not self-tolerant. The minor epitope escapes the induction of tolerance to self proteins more easily than the major epitopes, since we cannot elicit proliferative response to the major epitope. A striking feature of our results howev er is that lack of self tolerance to the minor epitope appears as not being due to the failure of presentation of this epitope in normal, he althy animals.