ZP3
Zona pellucida sperm-binding protein 3 precursor (Sperm receptor) (ZP3A/ZP3B) (Zona pellucida glycoprotein 3) (Zp-3) (Zona pellucida protein C) [Contains: Processed zona pellucida sperm-binding protein 3] [ZP3A] [ZP3B] [ZPC]
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Although human maternal autoantibodies may transfer transient manifestation of autoimmune disease to their progeny, some neonatal autoimmune diseases can progress, leading to the loss of tissue structure and function. In this study we document that murine maternal autoantibody transmitted to progeny can trigger de novo neonatal pathogenic autoreactive T cell response and T cell-mediated organ-specific autoimmune disease. Autoantibody to a zona pellucida 3 (ZP3) epitope was found to induce autoimmune ovarian disease (AOD) and premature ovarian failure in neonatal, but not adult, mice. Neonatal AOD did not occur in T cell-deficient pups, and the ovarian pathology was transferable by CD4( ) T cells from diseased donors. Interestingly, neonatal AOD occurred only in pups exposed to ZP3 autoantibody from neonatal days 1-5, but not from day 7 or day 9. The disease susceptibility neonatal time window was not related to a propensity of neonatal ovaries to autoimmune inflammation, and it was not affected by infusion of functional adult CD4( )CD25( ) T cells. However, resistance to neonatal AOD in 9-day-old mice was abrogated by CD4( )CD25( ) T cell depletion. Finally, neonatal AOD was blocked by Ab to IgG-FcR, and interestingly, the disease was not elicited by autoantibody to a second, independent native ZP3 B cell epitope. Therefore, a new mechanism of neonatal autoimmunity is presented in which epitope-specific autoantibody stimulates de novo autoimmune pathogenic CD4( ) T cell response.
MeSH Terms
- Administration, Oral
- Adoptive Transfer
- Aging
- Amino Acid Sequence
- Animals
- Animals, Newborn
- Autoantibodies
- Autoantigens
- Autoimmune Diseases
- CD4-Positive T-Lymphocytes
- Disease Progression
- Disease Susceptibility
- Dose-Response Relationship, Immunologic
- Egg Proteins
- Epitopes, B-Lymphocyte
- Female
- Immunity, Innate
- Immunohistochemistry
- Immunophenotyping
- Lymphocyte Depletion
- Male
- Maternal-Fetal Exchange
- Membrane Glycoproteins
- Mice
- Mice, Inbred A
- Mice, Inbred C57BL
- Milk
- Molecular Sequence Data
- Organ Specificity
- Ovarian Diseases
- Peptide Fragments
- Pregnancy
- Receptors, Cell Surface
- Receptors, IgG
- Receptors, Interleukin-2
- T-Lymphocyte Subsets
- Zona Pellucida
- Zona Pellucida Glycoproteins
A cDNA (rc75) encoding a 75-kDa rabbit zona pellucida (ZP) glycoprotein (R75) has been cloned and sequenced. The predicted amino acid sequence consists of 676 amino acids including seven potential N-glycosylation sites. The cDNA hybridizes to a 2.4-kilobase mRNA in ovary that is not detectable in other rabbit tissues. The R75 mRNA was also found to be expressed during the early stages of rabbit ovarian development (2-6 weeks of age) when the ovary contains primordial, primary, and early secondary follicles. The deduced amino acid sequence of rc75 has 77% similarity to the mouse ZP2 protein but no similarity to mouse ZP3. R75 also contains regions with 35-55% similarity to a previously cloned rabbit 55-kDa ZP protein. Monte Carlo simulation comparison confirmed that R75 has a significant probability of homology with mouse ZP2 and the rabbit 55-kDa ZP protein. Antibodies were developed against a fragment of R75 (rc75a cDNA) expressed in the pEX expression vector. These antibodies were used to confirm that the expressed protein contained epitopes found in the native rabbit ZP glycoprotein. These data suggest that some, but not all, ZP proteins may be conserved among different species and that within a species ZP proteins may share similar regions.
MeSH Terms
- Aging
- Amino Acid Sequence
- Animals
- Base Sequence
- Blotting, Northern
- Cloning, Molecular
- DNA
- Egg Proteins
- Female
- Membrane Glycoproteins
- Molecular Sequence Data
- Molecular Weight
- Ovary
- Protein Structure, Secondary
- RNA
- RNA, Messenger
- Rabbits
- Receptors, Cell Surface
- Recombinant Proteins
- Sequence Homology, Amino Acid
- Zona Pellucida
- Zona Pellucida Glycoproteins