CpG-containing oligodeoxynucleotide 1826 converts the weak uveitogenic rat interphotoreceptor retinoid-binding protein peptide 1181-1191 into a strong uveitogen.
Aberrant activation of autoreactive T cells is one of the major causes of autoimmune disease. Autoantigens are sequestered and in many cases weak immunogens. For example, in experimental autoimmune uveitis, immunization of naive rats with autologous interphotoreceptor retinoid-binding protein (IRBP) fails to induce intraocular inflammation or a strong T cell response, whereas bovine IRBP is a strong inducer of experimental autoimmune uveitis. Such observations challenge the view that the autoantigen alone is responsible for the development of autoimmunity. Here, we demonstrate that autologous rat IRBP is converted to a strong immunogen in the presence of a small dose of CpG-containing oligodeoxynucleotides. Our results indicate that specific CpG-containing oligodeoxynucleotides may play an important role in the activation and expansion of autoreactive T cells in vivo, leading to autoimmune disease.
Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, KY 40202, USA.
Hui
H
Shao
Song
S
Lei
Sheher L
SL
Sun
Jim
J
Xiang
Henry J
HJ
Kaplan
Deming
D
Sun
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D001327:Autoimmune Diseases / Q000276:immunology; D002417:Cattle; D002460:Cell Line; D018899:CpG Islands / Q000276:immunology; D004247:DNA / Q000008:administration & dosage / Q000494:pharmacology*; D004306:Dose-Response Relationship, Immunologic; D004338:Drug Combinations; D005136:Eye Proteins; D005260:Female; D008213:Lymphocyte Activation / Q000187:drug effects; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D012177:Retinol-Binding Proteins / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism* / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation; D014605:Uveitis / Q000276:immunology*; D000099214:Retinol-Binding Proteins, Interstitial
D000276:Adjuvants, Immunologic; D001324:Autoantigens; D004247:DNA; D004338:Drug Combinations; D005136:Eye Proteins; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial; C423449:CpG ODN 1826