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Related Experiment Videos

A pathogenic autoimmune process targeted at a surrogate epitope

A T Kozhich1, Y Kawano, C E Egwuagu

  • 1Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892.

The Journal of Experimental Medicine
|July 1, 1994
PubMed
Summary
This summary is machine-generated.

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Experimental autoimmune uveoretinitis (EAU) is induced by interphotoreceptor retinoid-binding protein (IRBP). Rat IRBP sequence 1181-1191 does not induce EAU in Lewis rats, unlike its bovine counterpart. Instead, rat IRBP sequence 273-283 is identified as the uveitogenic determinant.

Area of Science:

  • Ophthalmology
  • Immunology
  • Protein Chemistry

Background:

  • Interphotoreceptor retinoid-binding protein (IRBP) immunization causes experimental autoimmune uveoretinitis (EAU) in animals.
  • Bovine IRBP sequence 1181-1191 is immunodominant and uveitogenic in Lewis rats.
  • Rat IRBP sequence 1181-1191 differs from the bovine sequence at key residues.

Purpose of the Study:

  • To investigate the uveitogenic and immunogenic potential of rat IRBP sequence 1181-1191 in Lewis rats.
  • To identify the specific rat IRBP epitope responsible for inducing EAU.
  • To understand the mechanism of immune recognition in EAU.

Main Methods:

  • Immunization of Lewis rats with bovine and rat IRBP sequences.
  • Assessment of EAU induction and immune response.

Related Experiment Videos

  • Analysis of T-cell proliferation and signal transduction.
  • Competition assays for antigen-presenting cell binding.

    • Main Results:

    • Rat IRBP sequence 1181-1191 failed to induce EAU or an immune response in Lewis rats.
    • Rat IRBP sequence 1181-1191 exhibited poor binding to antigen-presenting cells.
    • Rat IRBP sequence 273-283, conserved between bovine and rat, was recognized by sensitized lymphocytes and induced uveitogenicity.
    • Rat IRBP sequence 273-283 demonstrated superior uveitogenic capacity compared to bovine IRBP sequence 1181-1191.

    Conclusions:

    • Rat IRBP sequence 1181-1191 is not the target for EAU-inducing lymphocytes in Lewis rats.
    • Rat IRBP sequence 273-283 acts as a "surrogate" determinant, triggering EAU in rats sensitized to bovine IRBP.
    • This study reveals a novel system where an autologous epitope homologue is inactive, and a different determinant is targeted in autoimmune eye disease.