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. 1995 Oct 1;182(4):1121–1131. doi: 10.1084/jem.182.4.1121

Molecular and immunological characterization of hr44, a human ocular component immunologically cross-reactive with antigen Ov39 of Onchocerca volvulus

PMCID: PMC2192280  PMID: 7561685

Abstract

Structural similarities between host self-antigens and infectious organisms may be involved in the expression of autoimmune reactivity and development of autoimmune disease. The unique eye pathology associated with Onchocerca volvulus infection, particularly the development of posterior segment lesions, may be promoted by such autoreactive responses. Ov39 is a parasite-derived antigen that has been shown previously to be antigenically cross-reactive with a 44,000- M(r) host ocular component. A clone, designated hr44, was isolated from a cDNA library of human retina by immunoscreen using serum to Ov39. A monoclonal antibody raised to Ov39 also reacted with hr44 and gave evidence for a shared conformational epitope. The primary structure analysis showed that identities between the antigens are limited and confined to small peptides. The cross-reactivity between the antigens appears to involve T cells, since Ov39-specific T cells can be stimulated by hr44, a neural-specific antigen. Based on secondary structure prediction, hr44 has the typical features of a membrane- associated type I antigen with an amino-terminal extracellular domain. mAbs and antisera localized the antigen in the optic nerve, neural retina, retinal pigment epithelium, as well as the epithelial layers of ciliary body and iris.

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Selected References

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  1. Abiose A., Jones B. R., Cousens S. N., Murdoch I., Cassels-Brown A., Babalola O. E., Alexander N. D., Nuhu I., Evans J., Ibrahim U. F. Reduction in incidence of optic nerve disease with annual ivermectin to control onchocerciasis. Lancet. 1993 Jan 16;341(8838):130–134. doi: 10.1016/0140-6736(93)90002-x. [DOI] [PubMed] [Google Scholar]
  2. Anderson J., Fuglsang H., Marshall T. F., Radolowicz A., Vaughan J. P. Studies on onchocerciasis in the United Cameroon Republic. IV. A four-year follow-up of six rain-forest and six savanna villages. The incidence of ocular lesions. Trans R Soc Trop Med Hyg. 1978;72(5):513–515. doi: 10.1016/0035-9203(78)90172-4. [DOI] [PubMed] [Google Scholar]
  3. Baum H., Butler P., Davies H., Sternberg M. J., Burroughs A. K. Autoimmune disease and molecular mimicry: an hypothesis. Trends Biochem Sci. 1993 Apr;18(4):140–144. doi: 10.1016/0968-0004(93)90022-f. [DOI] [PubMed] [Google Scholar]
  4. Ben-Nun A., Wekerle H., Cohen I. R. The rapid isolation of clonable antigen-specific T lymphocyte lines capable of mediating autoimmune encephalomyelitis. Eur J Immunol. 1981 Mar;11(3):195–199. doi: 10.1002/eji.1830110307. [DOI] [PubMed] [Google Scholar]
  5. Bird A. C., Anderson J., Fuglsang H. Morphology of posterior segment lesions of the eye in patients with onchocerciasis. Br J Ophthalmol. 1976 Jan;60(1):2–20. doi: 10.1136/bjo.60.1.2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bourdon M. A., Krusius T., Campbell S., Schwartz N. B., Ruoslahti E. Identification and synthesis of a recognition signal for the attachment of glycosaminoglycans to proteins. Proc Natl Acad Sci U S A. 1987 May;84(10):3194–3198. doi: 10.1073/pnas.84.10.3194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Braun G., McKechnie N. M., Connor V., Gilbert C. E., Engelbrecht F., Whitworth J. A., Taylor D. W. Immunological crossreactivity between a cloned antigen of Onchocerca volvulus and a component of the retinal pigment epithelium. J Exp Med. 1991 Jul 1;174(1):169–177. doi: 10.1084/jem.174.1.169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chan C. C., Nussenblatt R. B., Kim M. K., Palestine A. G., Awadzi K., Ottesen E. A. Immunopathology of ocular onchocerciasis. 2. Anti-retinal autoantibodies in serum and ocular fluids. Ophthalmology. 1987 Apr;94(4):439–443. doi: 10.1016/s0161-6420(87)33452-9. [DOI] [PubMed] [Google Scholar]
  9. Chan C. C., Ottesen E. A., Awadzi K., Badu R., Nussenblatt R. B. Immunopathology of ocular onchocerciasis. I. Inflammatory cells infiltrating the anterior segment. Clin Exp Immunol. 1989 Sep;77(3):367–372. [PMC free article] [PubMed] [Google Scholar]
  10. Chou P. Y., Fasman G. D. Prediction of the secondary structure of proteins from their amino acid sequence. Adv Enzymol Relat Areas Mol Biol. 1978;47:45–148. doi: 10.1002/9780470122921.ch2. [DOI] [PubMed] [Google Scholar]
  11. Dalbey R. E. Positively charged residues are important determinants of membrane protein topology. Trends Biochem Sci. 1990 Jul;15(7):253–257. doi: 10.1016/0968-0004(90)90047-f. [DOI] [PubMed] [Google Scholar]
  12. Damian R. T. Molecular mimicry: parasite evasion and host defense. Curr Top Microbiol Immunol. 1989;145:101–115. doi: 10.1007/978-3-642-74594-2_9. [DOI] [PubMed] [Google Scholar]
  13. Davies A., Lachmann P. J. Membrane defence against complement lysis: the structure and biological properties of CD59. Immunol Res. 1993;12(3):258–275. doi: 10.1007/BF02918257. [DOI] [PubMed] [Google Scholar]
  14. Deng H., Fosdick L., Sercarz E. The involvement of antigen processing in determinant selection by class II MHC and its relationship to immunodominance. APMIS. 1993 Sep;101(9):655–662. doi: 10.1111/j.1699-0463.1993.tb00161.x. [DOI] [PubMed] [Google Scholar]
  15. Ferguson M. A., Williams A. F. Cell-surface anchoring of proteins via glycosyl-phosphatidylinositol structures. Annu Rev Biochem. 1988;57:285–320. doi: 10.1146/annurev.bi.57.070188.001441. [DOI] [PubMed] [Google Scholar]
  16. Galfrè G., Milstein C. Preparation of monoclonal antibodies: strategies and procedures. Methods Enzymol. 1981;73(Pt B):3–46. doi: 10.1016/0076-6879(81)73054-4. [DOI] [PubMed] [Google Scholar]
  17. Gammon G., Sercarz E. E., Benichou G. The dominant self and the cryptic self: shaping the autoreactive T-cell repertoire. Immunol Today. 1991 Jun;12(6):193–195. doi: 10.1016/0167-5699(91)90052-U. [DOI] [PubMed] [Google Scholar]
  18. Gammon G., Sercarz E. How some T cells escape tolerance induction. Nature. 1989 Nov 9;342(6246):183–185. doi: 10.1038/342183a0. [DOI] [PubMed] [Google Scholar]
  19. Garner A. Pathology of ocular onchocerciasis: human and experimental. Trans R Soc Trop Med Hyg. 1976;70(5-6):374–377. doi: 10.1016/0035-9203(76)90113-9. [DOI] [PubMed] [Google Scholar]
  20. Garnier J., Osguthorpe D. J., Robson B. Analysis of the accuracy and implications of simple methods for predicting the secondary structure of globular proteins. J Mol Biol. 1978 Mar 25;120(1):97–120. doi: 10.1016/0022-2836(78)90297-8. [DOI] [PubMed] [Google Scholar]
  21. Guest J. R., Lewis H. M., Graham L. D., Packman L. C., Perham R. N. Genetic reconstruction and functional analysis of the repeating lipoyl domains in the pyruvate dehydrogenase multienzyme complex of Escherichia coli. J Mol Biol. 1985 Oct 20;185(4):743–754. doi: 10.1016/0022-2836(85)90059-2. [DOI] [PubMed] [Google Scholar]
  22. Hall R. Molecular mimicry. Adv Parasitol. 1994;34:81–132. doi: 10.1016/s0065-308x(08)60137-2. [DOI] [PubMed] [Google Scholar]
  23. Hopp T. P., Woods K. R. Prediction of protein antigenic determinants from amino acid sequences. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3824–3828. doi: 10.1073/pnas.78.6.3824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kearney J. F., Radbruch A., Liesegang B., Rajewsky K. A new mouse myeloma cell line that has lost immunoglobulin expression but permits the construction of antibody-secreting hybrid cell lines. J Immunol. 1979 Oct;123(4):1548–1550. [PubMed] [Google Scholar]
  25. Kehry M., Ewald S., Douglas R., Sibley C., Raschke W., Fambrough D., Hood L. The immunoglobulin mu chains of membrane-bound and secreted IgM molecules differ in their C-terminal segments. Cell. 1980 Sep;21(2):393–406. doi: 10.1016/0092-8674(80)90476-6. [DOI] [PubMed] [Google Scholar]
  26. Lehmann P. V., Forsthuber T., Miller A., Sercarz E. E. Spreading of T-cell autoimmunity to cryptic determinants of an autoantigen. Nature. 1992 Jul 9;358(6382):155–157. doi: 10.1038/358155a0. [DOI] [PubMed] [Google Scholar]
  27. Lin R. H., Mamula M. J., Hardin J. A., Janeway C. A., Jr Induction of autoreactive B cells allows priming of autoreactive T cells. J Exp Med. 1991 Jun 1;173(6):1433–1439. doi: 10.1084/jem.173.6.1433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Maddox P. H., Jenkins D. 3-Aminopropyltriethoxysilane (APES): a new advance in section adhesion. J Clin Pathol. 1987 Oct;40(10):1256–1257. doi: 10.1136/jcp.40.10.1256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. McKechnie N. M., Braun G., Connor V., Kläger S., Taylor D. W., Alexander R. A., Gilbert C. E. Immunologic cross-reactivity in the pathogenesis of ocular onchocerciasis. Invest Ophthalmol Vis Sci. 1993 Sep;34(10):2888–2902. [PubMed] [Google Scholar]
  30. McMahon J. E., Sowa S. I., Maude G. H., Kirkwood B. R. Onchocerciasis in Sierra Leone.2: A comparison of forest and savanna villages. Trans R Soc Trop Med Hyg. 1988;82(4):595–600. doi: 10.1016/0035-9203(88)90524-x. [DOI] [PubMed] [Google Scholar]
  31. Newland H. S., White A. T., Greene B. M., Murphy R. P., Taylor H. R. Ocular manifestations of onchocerciasis in a rain forest area of west Africa. Br J Ophthalmol. 1991 Mar;75(3):163–169. doi: 10.1136/bjo.75.3.163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Pearson W. R., Lipman D. J. Improved tools for biological sequence comparison. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2444–2448. doi: 10.1073/pnas.85.8.2444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Remme J., Dadzie K. Y., Rolland A., Thylefors B. Ocular onchocerciasis and intensity of infection in the community. I. West African savanna. Trop Med Parasitol. 1989 Sep;40(3):340–347. [PubMed] [Google Scholar]
  34. Rudensky AYu, Preston-Hurlburt P., Hong S. C., Barlow A., Janeway C. A., Jr Sequence analysis of peptides bound to MHC class II molecules. Nature. 1991 Oct 17;353(6345):622–627. doi: 10.1038/353622a0. [DOI] [PubMed] [Google Scholar]
  35. Saunders S., Jalkanen M., O'Farrell S., Bernfield M. Molecular cloning of syndecan, an integral membrane proteoglycan. J Cell Biol. 1989 Apr;108(4):1547–1556. doi: 10.1083/jcb.108.4.1547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Schneewind O., Jones K. F., Fischetti V. A. Sequence and structural characteristics of the trypsin-resistant T6 surface protein of group A streptococci. J Bacteriol. 1990 Jun;172(6):3310–3317. doi: 10.1128/jb.172.6.3310-3317.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Semba R. D., Murphy R. P., Newland H. S., Awadzi K., Greene B. M., Taylor H. R. Longitudinal study of lesions of the posterior segment in onchocerciasis. Ophthalmology. 1990 Oct;97(10):1334–1341. doi: 10.1016/s0161-6420(90)32413-2. [DOI] [PubMed] [Google Scholar]
  38. Sipos L., von Heijne G. Predicting the topology of eukaryotic membrane proteins. Eur J Biochem. 1993 May 1;213(3):1333–1340. doi: 10.1111/j.1432-1033.1993.tb17885.x. [DOI] [PubMed] [Google Scholar]
  39. Tomita M., Furthmayr H., Marchesi V. T. Primary structure of human erythrocyte glycophorin A. Isolation and characterization of peptides and complete amino acid sequence. Biochemistry. 1978 Oct 31;17(22):4756–4770. doi: 10.1021/bi00615a025. [DOI] [PubMed] [Google Scholar]
  40. 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]
  41. Wing M. G., Zajicek J., Seilly D. J., Compston D. A., Lachmann P. J. Oligodendrocytes lack glycolipid anchored proteins which protect them against complement lysis. Restoration of resistance to lysis by incorporation of CD59. Immunology. 1992 May;76(1):140–145. [PMC free article] [PubMed] [Google Scholar]
  42. Young R. W., Bok D. Participation of the retinal pigment epithelium in the rod outer segment renewal process. J Cell Biol. 1969 Aug;42(2):392–403. doi: 10.1083/jcb.42.2.392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. von Heijne G. Membrane protein assembly: rules of the game. Bioessays. 1995 Jan;17(1):25–30. doi: 10.1002/bies.950170107. [DOI] [PubMed] [Google Scholar]
  44. von Heijne G. Membrane proteins: from sequence to structure. Annu Rev Biophys Biomol Struct. 1994;23:167–192. doi: 10.1146/annurev.bb.23.060194.001123. [DOI] [PubMed] [Google Scholar]

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