Identification of a new epitope of human IRBP that induces autoimmune uveoretinitis in mice of the H-2b haplotype.
OBJECTIVE
Experimental autoimmune uveoretinitis (EAU) is a T-cell-mediated disease induced by immunization with interphotoreceptor retinoid binding protein (IRBP). Major uveitogenic sites have been identified for mice of the H-2r and H-2k haplotypes but not for the H-2b haplotype. The present communication describes the characterization of an epitope contained in residues 1 to 20 of human IRBP that induces EAU in H-2b mice.


METHODS
H-2b (C57BL/6, 129/J) and H-2r (BIO.RIII) mice were immunized with peptide 1-20 or with whole (bovine) IRBP. EAU (histopathology) and immunologic responses (delayed-type hypersensitivity [DTH], lymphocyte proliferation, and cytokine production) were assessed after 21 days.


RESULTS
C57BL/6 mice, 129/J and (129/JxC57BL/6)F1 mice, immunized with 200 to 300 microg of peptide, developed DTH and EAU with scores comparable to those induced by 100 microg IRBP. Their lymphocytes proliferated to the peptide and produced interferon-gamma (but not interleukin-4) and transferred EAU to syngeneic recipients. Lymphocytes of IRBP-immunized mice also responded to the peptide. Peptide 1-20-immunized B1O.RIII mice failed to develop either disease or immunologic responses. CONCLUSIONS. Human IRBP peptide 1-20 contains a major epitope for the H-2b haplotype, which is apparently not presented by the H-2r haplotype.
Avichezer
D
D
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-1857, USA.
Silver
P B
PB
Chan
C C
CC
Wiggert
B
B
Caspi
R R
RR
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D002417:Cattle; D016207:Cytokines / Q000096:biosynthesis; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D005136:Eye Proteins / Q000737:chemistry / Q000276:immunology*; D006183:H-2 Antigens / Q000276:immunology*; D006239:Haplotypes / Q000276:immunology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000209:etiology / Q000276:immunology / Q000473:pathology; D007114:Immunization; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D012173:Retinitis / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D012177:Retinol-Binding Proteins / Q000737:chemistry / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014605:Uveitis / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D000099214:Retinol-Binding Proteins, Interstitial
D016207:Cytokines; D000939:Epitopes; D005136:Eye Proteins; D006183:H-2 Antigens; D010446:Peptide Fragments; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial