title: Persistence of physiological self antigen is required for the regulation of self tolerance.
abstract: Endogenous Ag requirement for induction and maintenance of T cell tolerance has been extensively investigated in mice that express a transgenic Ag and/or its cognate transgenic TCR. In contrast, studies on tolerance for physiologically expressed self Ag and normal T cells are limited. Herein, we showed that the murine ovarian-specific ZP3 Ag is detectable from birth. Tolerance to ZP3 is detected in female relative to male mice. In comparison to males, 100-fold more ovarian peptide (pZP3) is required to elicit a comparable pathogenic response in females. Female tolerance to pZP3 was dependent on the presence of endogenous ovarian Ag, because neonatal ovariectomy converted the female response to that of males. Moreover, in female mice that were ovariectomized from the ages of 1-6 wk, the pZP3 responses were enhanced to the male level if ovaries were removed up to 7 days, but not 3 days, before adult challenge with pZP3. Thus, the physiologically expressed ZP3 Ag induces tolerance to pZP3, and the maintenance of tolerance is critically dependent on the continuous presence of the endogenous ovarian Ag. In contrast, exposure to endogenous ovarian Ag confined to the neonatal period is insufficient for the induction and maintenance of tolerance to ZP3.
authors.affiliation: Departments of Microbiology and Pathology, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Garza
authors.forename: S S
authors.initials: SS
authors.lastname: Agersborg
authors.forename: E
authors.initials: E
authors.lastname: Baker
authors.forename: K S
authors.initials: KS
authors.lastname: Tung
mesh_terms: D000367:Age Factors; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000276:immunology / Q000378:metabolism; D001324:Autoantigens / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D004527:Egg Proteins / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D005260:Female; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009869:Oophoritis / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface; D017634:Self Tolerance / Q000276:immunology*; D012727:Sex Characteristics; D013997:Time Factors; D015044:Zona Pellucida / Q000276:immunology / Q000378:metabolism; D000072216:Zona Pellucida Glycoproteins
chemical_list: D001324:Autoantigens; D004527:Egg Proteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D000072216:Zona Pellucida Glycoproteins; C000606521:Zp3 protein, mouse