Contraceptive vaccine assessment based on a murine ZP3 mini-autoantigen.
A summary is presented of published and some unpublished observations from studies on the immunological response of mice to a 13-mer peptide of the murine ovarian zona pellucida glycoprotein ZP3. The findings have the following implications for the design of immunocontraceptive vaccines. To be reversible, a ZP3 vaccine must not contain pathogenic T cell epitopes of ZP3, but contraception without autoimmune oophoritis may be feasible. The immune response to the ZP3 mini-autoantigen is highly variable among inbred mouse strains, suggesting that a single oophoritogenic peptide would not achieve irreversible contraception in an outbred population. The discovery of antigen mimicry at the level of T cell peptide has thrown doubt on the validity of current strategy in detecting relevant self-antigens that might cross react with vaccine immunogens and on the feasibility of fully predicting the cross-reactive autoimmunogenic potential of a peptide or polypeptide vaccine antigen. Autoantibodies directed against epitopes outside the ZP3 mini-autoantigen, produced by immunization with the pure T cell epitope, react with high affinity, with native zona pellucida, and may be useful in identifying B cell epitopes in ZP3.
Tung
K S
KS
Department of Pathology, University of Virginia, Charlottesville 22901.
Lou
Y H
YH
Luo
A M
AM
Ang
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology*; D003269:Contraception, Immunologic; D004527:Egg Proteins / Q000737:chemistry / Q000276:immunology*; D000939:Epitopes; D005260:Female; D007111:Immunity, Cellular; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009869:Oophoritis / Q000276:immunology; D011956:Receptors, Cell Surface; D013601:T-Lymphocytes / Q000276:immunology; D014612:Vaccines; D000072216:Zona Pellucida Glycoproteins
D001324:Autoantigens; D004527:Egg Proteins; D000939:Epitopes; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D014612:Vaccines; D000072216:Zona Pellucida Glycoproteins; C000606521:Zp3 protein, mouse