A shared epitope of the interphotoreceptor retinoid-binding protein recognized by the CD4+ and CD8+ autoreactive T cells.
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.
Shao
Hui
H
Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, KY 40202, USA.
Peng
Yong
Y
Liao
Tianjiang
T
Wang
Meiqin
M
Song
Ming
M
Kaplan
Henry J
HJ
Sun
Deming
D
D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D002469:Cell Separation; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism*; D005136:Eye Proteins / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism; D064532:Histocompatibility Antigen H-2D; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D012177:Retinol-Binding Proteins / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism*; D014605:Uveitis / Q000276:immunology / Q000473:pathology; D000099214:Retinol-Binding Proteins, Interstitial
D018984:Epitopes, T-Lymphocyte; D005136:Eye Proteins; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D010446:Peptide Fragments; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial