Interphotoreceptor retinoid-binding protein (IRBP)-deficient C57BL/6 mice have enhanced immunological and immunopathogenic responses to IRBP and an altered recognition of IRBP epitopes

Dody Avichezer, Gregory I. Liou, Chi Chao Chan, Giavonni M. Lewis, Barbara Wiggert, Larry A. Donoso, John M. Nickerson, Mary Alice Crawford, Rachel R. Caspi

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Experimental autoimmune uveitis (EAU) and pinealitis (EAP) can be induced in susceptible mice by immunization with immunologically privileged retinal antigens. In the present study, we analyzed the immunologic and immunopathologic responses of mice deficient in the retinal autoantigen interphotoreceptor retinoid-binding protein (IRBP). The consequences of IRBP deficiency on the T-cell repertoire were also investigated. IRBP+/+, IRBP+/-and IRBP-/-mice on the C57BL/6 background were immunized with IRBP or with a pathogenic epitope, IRBP(1-20) peptide in adjuvant, and were evaluated for disease severity and immunological responses. C57BL/6 IRBP-/-mice were completely resistant to EAU and EAP, and had enhanced immunological responses to IRBP and to its pathogenic peptide 1-20, as compared to their IRBP+/+counterparts. IRBP-/-mice exhibited an altered IRBP epitope recognition. T cell epitope mapping revealed a response to IRBP peptide 271-290 in IRBP-/-mice, that was absent in the wild type. Primed T cells of IRBP-/-mice transferred an exacerbated form of EAU to naïve wild type recipients. A gene-dose effect was evident in that C57BL/6 IRBP+/-mice, exhibited intermediate immunological responses and lower disease scores compared to wild type. We conclude that expression of IRBP in target tissues is a necessary prerequisite for disease induction, excluding other retinoid-binding or vision-related proteins as surrogate targets. Furthermore, endogenous expression of IRBP is directly responsible for lowering the threshold of susceptibility to uveitic disease.

Original languageEnglish (US)
Pages (from-to)185-194
Number of pages10
JournalJournal of Autoimmunity
Volume21
Issue number3
DOIs
StatePublished - Jan 1 2003

Keywords

  • Autoimmune disease
  • Central tolerance
  • Experimental autoimmune uveitis
  • Immune privilege
  • Pinealitis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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