title: Mimicry epitope from Ehrlichia canis for interphotoreceptor retinoid-binding protein 201-216 prevents autoimmune uveoretinitis by acting as altered peptide ligand.
abstract: We report here identification of novel mimicry epitopes for interphotoreceptor retinoid-binding protein (IRBP) 201-216, a candidate ocular antigen that causes experimental autoimmune uveoretinitis (EAU) in A/J mice. One mimicry epitope from Ehrlichia canis (EHC), designated EHC 44-59, induced cross-reactive T cells for IRBP 201-216 capable of producing T helper (Th)1 and Th17 cytokines, but failed to induce EAU in A/J mice. In addition, animals first primed with suboptimal doses of IRBP 201-216 and subsequently immunized with EHC 44-59 did not develop EAU; rather, the mimicry epitope prevented the disease induced by IRBP 201-216. However, alteration in the composition of EHC 44-59 by substituting alanine with valine at position 49, similar to the composition of IRBP 201-216, enabled the mimicry epitope to acquire uveitogenicity. The data provide new insights as to how microbes containing mimicry sequences for retinal antigens can prevent ocular inflammation by acting as naturally occurring altered peptide ligands.
authors.affiliation: School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, United States.
authors.forename: Arunakumar
authors.initials: A
authors.lastname: Gangaplara
authors.forename: Chandirasegaran
authors.initials: C
authors.lastname: Massilamany
authors.forename: David
authors.initials: D
authors.lastname: Steffen
authors.forename: Jay
authors.initials: J
authors.lastname: Reddy
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020274:Autoimmune Diseases of the Nervous System / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D002417:Cattle; D041061:Ehrlichia canis / Q000235:genetics / Q000276:immunology*; D016873:Ehrlichiosis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D005136:Eye Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D005260:Female; D008024:Ligands; D051379:Mice; D008805:Mice, Inbred A; D018716:Molecular Mimicry / Q000276:immunology*; D008969:Molecular Sequence Data; D012173:Retinitis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D012177:Retinol-Binding Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D014605:Uveitis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D005136:Eye Proteins; D008024:Ligands; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial
keywords: 7-AAD; 7-aminoactinomycin D; APL; Autoimmunity; CFA; CLIP; CLN; CTR; Chlamydia trachomatis; Clostridium novyi; Cross-reactive T cells; DELFIA; EAU; EHC; Ehrlichia canis; Experimental autoimmune uveoretinitis; HEC; HEL; IC(50); IFN; IL; IRBP; Interphotoreceptor retinoid-binding protein; LN; LNC; MHC; Molecular mimicry; PAB; PMA; PSP; PT; Paracoccidioides brasiliensis; Pseudomonas putida; RNase; RT; SA; T cell receptor; TCR; TRC; Trypanosoma cruzi; altered peptide ligand; bovine ribonuclease; class-II associated invariant chain peptide; complete Freund's adjuvant; counts per minute; cpm; dissociation-enhanced lanthanide fluoroimmunoassay; experimental autoimmune uveoretinitis; half maximal inhibitory concentration; hen egg white lysozyme; hepatitis C virus; interferon; interleukin; interphotoreceptor retinoid-binding protein; lymph node cells; lymph nodes; major histocompatibility complex; pertussis toxin; phorbol 12-myristate 13-acetate; room temperature; streptavidin; tet(+); tetramer positive