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
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Autoimmune Diseases / immunology
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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CD4-Positive T-Lymphocytes / transplantation
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / transplantation
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Cell Separation
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Epitopes, T-Lymphocyte / administration & dosage
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Epitopes, T-Lymphocyte / immunology
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Epitopes, T-Lymphocyte / metabolism*
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Eye Proteins / administration & dosage
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Eye Proteins / immunology
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Eye Proteins / metabolism*
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Female
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H-2 Antigens / immunology
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H-2 Antigens / metabolism
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Histocompatibility Antigen H-2D
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Lymphocyte Activation / immunology
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Mice
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Mice, Inbred C57BL
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Molecular Sequence Data
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Peptide Fragments / administration & dosage
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Peptide Fragments / immunology
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Peptide Fragments / metabolism
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Protein Binding / immunology
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Retinol-Binding Proteins / administration & dosage
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Retinol-Binding Proteins / immunology
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Retinol-Binding Proteins / metabolism*
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Uveitis / immunology
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Uveitis / pathology
Substances
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Epitopes, T-Lymphocyte
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Eye Proteins
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H-2 Antigens
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Histocompatibility Antigen H-2D
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Peptide Fragments
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Retinol-Binding Proteins
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interstitial retinol-binding protein