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. 1994 Aug;97(2):219–225. doi: 10.1111/j.1365-2249.1994.tb06071.x

Analysis of the uveitogenic determinant in repeat structure of retinal interphotoreceptor retinoid-binding protein (IRBP).

H Inoue 1, M Takeuchi 1, T Tanaka 1, M Usui 1, S Ando 1, O Taguchi 1
PMCID: PMC1534699  PMID: 8050169

Abstract

IRBP is a glycolipoprotein with a four-fold partially homologous repeat structure approximately 300 residues in length, and is one of the retinal antigens capable of inducing experimental autoimmune uveoretinitis (EAU) in susceptible animals by their active immunization. The most immunopathogenic peptide of bovine IRBP for EAU in Lewis rats is reported to be the sequence 1169-1191 (PTARSVGAADGSSWEGVGVVPDV) with two immunogenic motifs common to T cell epitopes (underlined). The uveitogenic site of peptide 1169-1191 was localized at the carboxyl terminus (peptide 1182-1191) and not at the amino acid terminus (peptide 1169-1182). Repeat peptides of sequence 1179-1191 containing the four homologous residues (1182W, 1186G, 1187V and 1189P), that is the peptides 271-283, 579-591 and 880-892, all elicited EAU. Peptide 579-591 could not stimulate proliferation of lymphocytes from rats immunized with IRBP, but had the capacity to adoptively transfer EAU. The role of the homologous residues was examined using analogues of the uveitogenic peptide 1182-1194, in which each homologous residue was substituted by glycine (G) or leucine (L) (1182W-->G, 1186G-->L, 1187V-->G, and 1189P-->G). One analogue (1186G-->L) strongly diminished the ability to induce EAU, while the other three analogues completely abolished the ability, indicating that these homologous residues were essential for the induction of EAU. In addition, the uveitogenic peptides tested in this study were found not to contain the major epitope for antibody production.

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Selected References

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  1. Allen P. M., Matsueda G. R., Evans R. J., Dunbar J. B., Jr, Marshall G. R., Unanue E. R. Identification of the T-cell and Ia contact residues of a T-cell antigenic epitope. 1987 Jun 25-Jul 1Nature. 327(6124):713–715. doi: 10.1038/327713a0. [DOI] [PubMed] [Google Scholar]
  2. Berzofsky J. A. Immunodominance in T lymphocyte recognition. Immunol Lett. 1988 Jun;18(2):83–92. doi: 10.1016/0165-2478(88)90046-6. [DOI] [PubMed] [Google Scholar]
  3. Borst D. E., Redmond T. M., Elser J. E., Gonda M. A., Wiggert B., Chader G. J., Nickerson J. M. Interphotoreceptor retinoid-binding protein. Gene characterization, protein repeat structure, and its evolution. J Biol Chem. 1989 Jan 15;264(2):1115–1123. [PubMed] [Google Scholar]
  4. Broekhuyse R. M., Winkens H. J., Kuhlmann E. D. Induction of experimental autoimmune uveoretinitis and pinealitis by IRBP. Comparison to uveoretinitis induced by S-antigen and opsin. Curr Eye Res. 1986 Mar;5(3):231–240. doi: 10.3109/02713688609020048. [DOI] [PubMed] [Google Scholar]
  5. Eisenfeld A. J., Bunt-Milam A. H., Saari J. C. Uveoretinitis in rabbits following immunization with interphotoreceptor retinoid-binding protein. Exp Eye Res. 1987 Mar;44(3):425–438. doi: 10.1016/s0014-4835(87)80176-8. [DOI] [PubMed] [Google Scholar]
  6. Faure J. P. Autoimmunity and the retina. Curr Top Eye Res. 1980;2:215–302. [PubMed] [Google Scholar]
  7. Fong S. L., Bridges C. D. Internal quadruplication in the structure of human interstitial retinol-binding protein deduced from its cloned cDNA. J Biol Chem. 1988 Oct 25;263(30):15330–15334. [PubMed] [Google Scholar]
  8. Fox G. M., Kuwabara T., Wiggert B., Redmond T. M., Hess H. H., Chader G. J., Gery I. Experimental autoimmune uveoretinitis (EAU) induced by retinal interphotoreceptor retinoid-binding protein (IRBP): differences between EAU induced by IRBP and by S-antigen. Clin Immunol Immunopathol. 1987 May;43(2):256–264. doi: 10.1016/0090-1229(87)90133-4. [DOI] [PubMed] [Google Scholar]
  9. Fox G. M., Redmond T. M., Wiggert B., Kuwabara T., Chader G. J., Gery I. Dissociation between lymphocyte activation for proliferation and for the capacity to adoptively transfer uveoretinitis. J Immunol. 1987 May 15;138(10):3242–3246. [PubMed] [Google Scholar]
  10. Gery I., Wiggert B., Redmond T. M., Kuwabara T., Crawford M. A., Vistica B. P., Chader G. J. Uveoretinitis and pinealitis induced by immunization with interphotoreceptor retinoid-binding protein. Invest Ophthalmol Vis Sci. 1986 Aug;27(8):1296–1300. [PubMed] [Google Scholar]
  11. Gregerson D. S., Fling S. P., Obritsch W. F., Merryman C. F., Donoso L. A. Identification of T cell recognition sites in S-antigen: dissociation of proliferative and pathogenic sites. Cell Immunol. 1989 Oct 15;123(2):427–440. doi: 10.1016/0008-8749(89)90302-x. [DOI] [PubMed] [Google Scholar]
  12. Hirose S., Kuwabara T., Nussenblatt R. B., Wiggert B., Redmond T. M., Gery I. Uveitis induced in primates by interphotoreceptor retinoid-binding protein. Arch Ophthalmol. 1986 Nov;104(11):1698–1702. doi: 10.1001/archopht.1986.01050230136049. [DOI] [PubMed] [Google Scholar]
  13. Hunter S. Experimental allergic encephalomyelitis: clinical disease and enhanced cellular transfer in the absence of lymphocyte proliferative responses against syngeneic MBP. Cell Immunol. 1986 Jan;97(1):204–209. doi: 10.1016/0008-8749(86)90390-4. [DOI] [PubMed] [Google Scholar]
  14. Ichikawa T., Taguchi O., Takahashi T., Ikeda H., Takeuchi M., Tanaka T., Usui M., Nishizuka Y. Spontaneous development of autoimmune uveoretinitis in nude mice following reconstitution with embryonic rat thymus. Clin Exp Immunol. 1991 Oct;86(1):112–117. doi: 10.1111/j.1365-2249.1991.tb05782.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kotake S., Redmond T. M., Wiggert B., Vistica B., Sanui H., Chader G. J., Gery I. Unusual immunologic properties of the uveitogenic interphotoreceptor retinoid-binding protein-derived peptide R23. Invest Ophthalmol Vis Sci. 1991 Jun;32(7):2058–2064. [PubMed] [Google Scholar]
  16. Kotake S., Wiggert B., Redmond T. M., Borst D. E., Nickerson J. M., Margalit H., Berzofsky J. A., Chader G. J., Gery I. Repeated determinants within the retinal interphotoreceptor retinoid-binding protein (IRBP): immunological properties of the repeats of an immunodominant determinant. Cell Immunol. 1990 Apr 1;126(2):331–342. doi: 10.1016/0008-8749(90)90325-l. [DOI] [PubMed] [Google Scholar]
  17. Kotake S., Wiggert B., Zhang X. Y., Redmond T. M., Chader G. J., Gery I. Stimulation in vitro of lymphocytes for induction of uveoretinitis without any significant proliferation. J Immunol. 1990 Jul 15;145(2):534–539. [PubMed] [Google Scholar]
  18. Mannie M. D., Paterson P. Y., U'Prichard D. C., Flouret G. Encephalitogenic and proliferative responses of Lewis rat lymphocytes distinguished by position 75- and 80-substituted peptides of myelin basic protein. J Immunol. 1989 Apr 15;142(8):2608–2616. [PubMed] [Google Scholar]
  19. Matsuo T., Nakayama T., Koyama T., Koyama M., Fujimoto S., Matsuo N. Immunological studies of uveitis. 3. Cell-mediated immunity to interphotoreceptor retinoid-binding protein. Jpn J Ophthalmol. 1986;30(4):487–494. [PubMed] [Google Scholar]
  20. Milich D. R., Hughes J. L., Houghten R., McLachlan A., Jones J. E. Functional identification of agretopic and epitopic residues within an HBcAg T cell determinant. J Immunol. 1989 Nov 15;143(10):3141–3147. [PubMed] [Google Scholar]
  21. Rothbard J. B., Taylor W. R. A sequence pattern common to T cell epitopes. EMBO J. 1988 Jan;7(1):93–100. doi: 10.1002/j.1460-2075.1988.tb02787.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sanui H., Redmond T. M., Hu L. H., Kuwabara T., Margalit H., Cornette J. L., Wiggert B., Chader G. J., Gery I. Synthetic peptides derived from IRBP induce EAU and EAP in Lewis rats. Curr Eye Res. 1988 Jul;7(7):727–735. doi: 10.3109/02713688809033202. [DOI] [PubMed] [Google Scholar]
  23. Sanui H., Redmond T. M., Kotake S., Wiggert B., Hu L. H., Margalit H., Berzofsky J. A., Chader G. J., Gery I. Identification of an immunodominant and highly immunopathogenic determinant in the retinal interphotoreceptor retinoid-binding protein (IRBP). J Exp Med. 1989 Jun 1;169(6):1947–1960. doi: 10.1084/jem.169.6.1947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Taguchi O., Takahashi T., Seto M., Namikawa R., Matsuyama M., Nishizuka Y. Development of multiple organ-localized autoimmune diseases in nude mice after reconstitution of T cell function by rat fetal thymus graft. J Exp Med. 1986 Jul 1;164(1):60–71. doi: 10.1084/jem.164.1.60. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Urban J. L., Horvath S. J., Hood L. Autoimmune T cells: immune recognition of normal and variant peptide epitopes and peptide-based therapy. Cell. 1989 Oct 20;59(2):257–271. doi: 10.1016/0092-8674(89)90288-2. [DOI] [PubMed] [Google Scholar]
  26. Van der Lelij A., Doekes G., Hwan B. S., Vetter J. C., Rietveld E., Stilma J. S., Kijlstra A. Humoral autoimmune response against S-antigen and IRBP in ocular onchocerciasis. Invest Ophthalmol Vis Sci. 1990 Jul;31(7):1374–1380. [PubMed] [Google Scholar]
  27. Wraith D. C., Smilek D. E., Mitchell D. J., Steinman L., McDevitt H. O. Antigen recognition in autoimmune encephalomyelitis and the potential for peptide-mediated immunotherapy. Cell. 1989 Oct 20;59(2):247–255. doi: 10.1016/0092-8674(89)90287-0. [DOI] [PubMed] [Google Scholar]

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