Skip to main content
NCBI home page
Immunology logoLink to Immunology
. 1993 Apr;78(4):586–591.

Human cartilage aggrecan CS1 region contains cryptic T-cell recognition sites.

J A Goodacre 1, S Middleton 1, S Lynn 1, D A Ross 1, J Pearson 1
PMCID: PMC1421889  PMID: 8388364

Abstract

Cartilage proteoglycan aggregates (PG) are candidate T-cell autoantigens in the pathogenesis of rheumatoid arthritis (RA). We have investigated the possibility that responses to class II-restricted T-cell recognition sites in human cartilage aggrecan (core protein) may depend upon whether these sites are available as free peptide antigens or as part of intact monomers. Analysis of mouse T-cell responses to intact or deglycosylated monomers, purified from human articular cartilage, and to synthetic peptides of the chondroitin sulphate (CS) attachment region homologous repeat sequence showed that recognition of T-cell epitopes in the CS1 region was strongly dependent upon the form of antigen used. The results show that the CS1 region contains cryptic T-cell recognition sites and raise the possibility that fragments of PG, released through the action of extracellular proteases in inflamed joints, may be capable of activating T cells with specificities for epitopes which are not made available following processing of intact PG. T cells with specificities for cryptic epitopes in PG may play a role in the pathogenesis of RA.

Full text

PDF
586

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bayliss M. T. Proteoglycan structure and metabolism during maturation and ageing of human articular cartilage. Biochem Soc Trans. 1990 Oct;18(5):799–802. doi: 10.1042/bst0180799. [DOI] [PubMed] [Google Scholar]
  2. Cox J. H., Ivanyi J., Young D. B., Lamb J. R., Syred A. D., Francis M. J. Orientation of epitopes influences the immunogenicity of synthetic peptide dimers. Eur J Immunol. 1988 Dec;18(12):2015–2019. doi: 10.1002/eji.1830181222. [DOI] [PubMed] [Google Scholar]
  3. Del Val M., Schlicht H. J., Ruppert T., Reddehase M. J., Koszinowski U. H. Efficient processing of an antigenic sequence for presentation by MHC class I molecules depends on its neighboring residues in the protein. Cell. 1991 Sep 20;66(6):1145–1153. doi: 10.1016/0092-8674(91)90037-y. [DOI] [PubMed] [Google Scholar]
  4. Doege K. J., Sasaki M., Kimura T., Yamada Y. Complete coding sequence and deduced primary structure of the human cartilage large aggregating proteoglycan, aggrecan. Human-specific repeats, and additional alternatively spliced forms. J Biol Chem. 1991 Jan 15;266(2):894–902. [PubMed] [Google Scholar]
  5. Dudhia J., Hardingham T. E. The primary structure of human cartilage link protein. Nucleic Acids Res. 1990 Mar 11;18(5):1292–1292. doi: 10.1093/nar/18.5.1292. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Edge A. S., Faltynek C. R., Hof L., Reichert L. E., Jr, Weber P. Deglycosylation of glycoproteins by trifluoromethanesulfonic acid. Anal Biochem. 1981 Nov 15;118(1):131–137. doi: 10.1016/0003-2697(81)90168-8. [DOI] [PubMed] [Google Scholar]
  7. Glant T. T., Fülöp C., Mikecz K., Buzás E., Molnár G., Erhardt P. Proteoglycan-specific autoreactive antibodies and T-lymphocytes in experimental arthritis and human rheumatoid joint diseases. Biochem Soc Trans. 1990 Oct;18(5):796–799. doi: 10.1042/bst0180796. [DOI] [PubMed] [Google Scholar]
  8. Glant T. T., Mikecz K., Arzoumanian A., Poole A. R. Proteoglycan-induced arthritis in BALB/c mice. Clinical features and histopathology. Arthritis Rheum. 1987 Feb;30(2):201–212. doi: 10.1002/art.1780300211. [DOI] [PubMed] [Google Scholar]
  9. Golvano J., Lasarte J. J., Sarobe P., Gullón A., Prieto J., Borrás-Cuesta F. Polarity of immunogens: implications for vaccine design. Eur J Immunol. 1990 Oct;20(10):2363–2366. doi: 10.1002/eji.1830201031. [DOI] [PubMed] [Google Scholar]
  10. Hughes C., Murphy G., Hardingham T. E. Metalloproteinase digestion of cartilage proteoglycan. Pattern of cleavage by stromelysin and susceptibility to collagenase. Biochem J. 1991 Nov 1;279(Pt 3):733–739. doi: 10.1042/bj2790733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Leroux J. Y., Poole A. R., Webber C., Vipparti V., Choi H. U., Rosenberg L. C., Banerjee S. Characterization of proteoglycan-reactive T cell lines and hybridomas from mice with proteoglycan-induced arthritis. J Immunol. 1992 Apr 1;148(7):2090–2096. [PubMed] [Google Scholar]
  12. Lipham W. J., Redmond T. M., Takahashi H., Berzofsky J. A., Wiggert B., Chader G. J., Gery I. Recognition of peptides that are immunopathogenic but cryptic. Mechanisms that allow lymphocytes sensitized against cryptic peptides to initiate pathogenic autoimmune processes. J Immunol. 1991 Jun 1;146(11):3757–3762. [PubMed] [Google Scholar]
  13. Martin H., Dean M. A proteolytic fragment from human link protein is taken up and processed by monocytes and B cells. Biochem J. 1991 Dec 15;280(Pt 3):679–686. doi: 10.1042/bj2800679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Mikecz K., Glant T. T., Baron M., Poole A. R. Isolation of proteoglycan-specific T lymphocytes from patients with ankylosing spondylitis. Cell Immunol. 1988 Mar;112(1):55–63. doi: 10.1016/0008-8749(88)90275-4. [DOI] [PubMed] [Google Scholar]
  15. Mikecz K., Glant T. T., Buzás E., Poole A. R. Proteoglycan-induced polyarthritis and spondylitis adoptively transferred to naive (nonimmunized) BALB/c mice. Arthritis Rheum. 1990 Jun;33(6):866–876. doi: 10.1002/art.1780330614. [DOI] [PubMed] [Google Scholar]
  16. Mikecz K., Glant T. T., Poole A. R. Immunity to cartilage proteoglycans in BALB/c mice with progressive polyarthritis and ankylosing spondylitis induced by injection of human cartilage proteoglycan. Arthritis Rheum. 1987 Mar;30(3):306–318. doi: 10.1002/art.1780300310. [DOI] [PubMed] [Google Scholar]
  17. Munesinghe D. Y., Clavijo P., Calle M. C., Nussenzweig R. S., Nardin E. Immunogenicity of multiple antigen peptides (MAP) containing T and B cell epitopes of the repeat region of the P. falciparum circumsporozoite protein. Eur J Immunol. 1991 Dec;21(12):3015–3020. doi: 10.1002/eji.1830211217. [DOI] [PubMed] [Google Scholar]
  18. Nguyen Q., Mort J. S., Roughley P. J. Cartilage proteoglycan aggregate is degraded more extensively by cathepsin L than by cathepsin B. Biochem J. 1990 Mar 1;266(2):569–573. [PMC free article] [PubMed] [Google Scholar]
  19. O'Sullivan D., Arrhenius T., Sidney J., Del Guercio M. F., Albertson M., Wall M., Oseroff C., Southwood S., Colón S. M., Gaeta F. C. On the interaction of promiscuous antigenic peptides with different DR alleles. Identification of common structural motifs. J Immunol. 1991 Oct 15;147(8):2663–2669. [PubMed] [Google Scholar]
  20. Perkins D. L., Berriz G., Kamradt T., Smith J. A., Gefter M. L. Immunodominance: intramolecular competition between T cell epitopes. J Immunol. 1991 Apr 1;146(7):2137–2144. [PubMed] [Google Scholar]
  21. Roughley P. J., White R. J. Age-related changes in the structure of the proteoglycan subunits from human articular cartilage. J Biol Chem. 1980 Jan 10;255(1):217–224. [PubMed] [Google Scholar]
  22. Sigal L. H., Johnston S. L., Phillips P. E. Cellular immune responses to cartilage components in rheumatoid arthritis and osteoarthritis: a review and report of a study. Clin Exp Rheumatol. 1988 Jan-Mar;6(1):59–66. [PubMed] [Google Scholar]
  23. Witter J., Roughley P. J., Webber C., Roberts N., Keystone E., Poole A. R. The immunologic detection and characterization of cartilage proteoglycan degradation products in synovial fluids of patients with arthritis. Arthritis Rheum. 1987 May;30(5):519–529. doi: 10.1002/art.1780300506. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES