FREQUENCY OF MOLECULAR MIMICRY AMONG T-CELL PEPTIDES AS THE BASIS FORAUTOIMMUNE-DISEASE AND AUTOANTIBODY INDUCTION

Experimental ovarian autoimmune disease is inducible by immunization w ith an ovarian peptide from zona pellucida (ZP) 3, a glycoprotein of t he zona pellucida on mouse oocyte. The murine ZP3 peptide contains two nested T cell epitopes with slightly different critical residue motif s. To investigate the frequency of cross-reaction between nonovarian a nd ovarian peptides, we have chosen arbitrarily 16 nonovarian peptides with complete or partial homology to the critical residue motifs of t he two T cell epitopes. Based on peptide induction of autoimmune oopho ritis and T cell-dependent amplified autoantibody response to ovarian ZP, cross-reaction was documented for 7 (or 44%) of the 16 nonovarian peptides studied. Thus, molecular mimicry as a pathogenetic mechanism of autoimmunity should not be limited by the frequency of cross-reacti on among self and nonself peptides. On the other hand, the sharing of critical residue motif per se is not sufficient for mimicry to occur, nor does it predict peptide cross-reaction.