Frequency of molecular mimicry among T cell peptides as the basis for autoimmune disease and autoantibody induction.
Experimental ovarian autoimmune disease is inducible by immunization with an ovarian peptide from zona pellucida (ZP) 3, a glycoprotein of the zona pellucida on mouse oocyte. The murine ZP3 peptide contains two nested T cell epitopes with slightly different critical residue motifs. To investigate the frequency of cross-reaction between nonovarian and ovarian peptides, we have chosen arbitrarily 16 nonovarian peptides with complete or partial homology to the critical residue motifs of the two T cell epitopes. Based on peptide induction of autoimmune oophoritis 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-reaction 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.
Garza
K M
KM
Department of Microbiology, University of Virginia, Charlottesville 22908, USA.
Tung
K S
KS
D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology*; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology*; D003429:Cross Reactions; D004527:Egg Proteins / Q000276:immunology*; D018604:Epitope Mapping / Q000379:methods; D005260:Female; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009869:Oophoritis / Q000209:etiology / Q000276:immunology; D011956:Receptors, Cell Surface; D013601:T-Lymphocytes / Q000276:immunology*; D000072216:Zona Pellucida Glycoproteins
D001323:Autoantibodies; D004527:Egg Proteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D000072216:Zona Pellucida Glycoproteins; C000606521:Zp3 protein, mouse