A shared epitope of the interphotoreceptor retinoid-binding protein recognized by the CD4+ and CD8+ autoreactive T cells

J Immunol. 2005 Aug 1;175(3):1851-7. doi: 10.4049/jimmunol.175.3.1851.

Abstract

We previously demonstrated that cultures of rat uveitogenic T cells rapidly become dominated by CD4+ cells, but activation of CD8+ autoreactive T cells also occurred during the in vitro culture of in vivo-primed T cells. In the present study, we show that the commonly used uveitogenic peptide, interphotoreceptor retinoid-binding protein (IRBP) 1-20, generated both CD4+ and CD8+ autoreactive T cells in the C57BL/6 (B6) mouse and that this 20-mer contains at least two distinct antigenic epitopes. To determine whether the CD8 response was Ag-specific and whether CD4+ and CD8+ IRBP1-20-specific T cells recognize distinct antigenic epitopes, we prepared highly purified CD4+ and CD8+ T cells from IRBP1-20-primed mice and tested their proliferative response to a large panel of truncated peptides derived from IRBP1-20. The results showed that both CD4+ and CD8+ T cells recognized the same spectrum of peptides. In addition, peptides P10-18 were found to bind effectively to CD8+ IRBP1-20-specific T cells when complexed with recombinant H-2K(b) and also stimulate the proliferation and cytokine production of CD4+ IRBP1-20-specific T cells. Our results document for the first time that CD8+ and CD4+ autoreactive T cells display characteristic epitope recognition and they both recognize the same core epitope.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Autoimmune Diseases / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / transplantation
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / transplantation
  • Cell Separation
  • Epitopes, T-Lymphocyte / administration & dosage
  • Epitopes, T-Lymphocyte / immunology
  • Epitopes, T-Lymphocyte / metabolism*
  • Eye Proteins / administration & dosage
  • Eye Proteins / immunology
  • Eye Proteins / metabolism*
  • Female
  • H-2 Antigens / immunology
  • H-2 Antigens / metabolism
  • Histocompatibility Antigen H-2D
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism
  • Protein Binding / immunology
  • Retinol-Binding Proteins / administration & dosage
  • Retinol-Binding Proteins / immunology
  • Retinol-Binding Proteins / metabolism*
  • Uveitis / immunology
  • Uveitis / pathology

Substances

  • Epitopes, T-Lymphocyte
  • Eye Proteins
  • H-2 Antigens
  • Histocompatibility Antigen H-2D
  • Peptide Fragments
  • Retinol-Binding Proteins
  • interstitial retinol-binding protein