Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1994 Aug 1;180(2):745–749. doi: 10.1084/jem.180.2.745

T cell recognition of carbohydrates on type II collagen

PMCID: PMC2191590  PMID: 8046350

Abstract

A critical event in an immune response is the T cell recognition of peptides bound to major histocompatibility complex (MHC) molecules on the surface of an antigen presenting cell (APC). Although the majority of eukaryotic proteins are glycosylated, it has not yet been shown that T cell recognition of such proteins involves recognition of the bound carbohydrates. Type II collagen (CII), the major protein constituent of joint cartilage, is posttranslationally modified by hydroxylation and glycosylation of lysines. In this report we show that posttranslational modifications of the immunodominant peptide CII(256-270) generate a structural determinant that is distinct from the determinant represented by the corresponding synthetic peptide. Elimination of carbohydrates, present on CII, by two different biochemical methods revealed that the carbohydrates, O-linked to the hydroxylysines within the CII(256-270) determinant, were crucial for the reactivity towards the posttranslationally modified peptide. Furthermore, a T cell hybridoma specific for the glycosylated determinant was stimulated by tryptic CII-peptides presented by fixed APCs, thus showing that the carbohydrates are involved in the trimolecular complex T cell receptor/peptide/MHC. Finally, the importance of the bound carbohydrates for the arthritogenicity of CII was investigated by comparing the development of arthritis after immunization with carbohydrate-depleted and glycosylated CII, respectively. Incidence, time of onset, and severity of the disease were significantly affected by the elimination of carbohydrates, whereas no significant difference in anti-CII antibody titers was seen.

Full Text

The Full Text of this article is available as a PDF (502.2 KB).

Selected References

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

  1. Andersson M., Cremer M. A., Terato K., Burkhardt H., Holmdahl R. Analysis of type II collagen reactive T cells in the mouse. II. Different localization of immunodominant T cell epitopes on heterologous and autologous type II collagen. Scand J Immunol. 1991 May;33(5):505–510. doi: 10.1111/j.1365-3083.1991.tb02520.x. [DOI] [PubMed] [Google Scholar]
  2. Chicz R. M., Urban R. G., Gorga J. C., Vignali D. A., Lane W. S., Strominger J. L. Specificity and promiscuity among naturally processed peptides bound to HLA-DR alleles. J Exp Med. 1993 Jul 1;178(1):27–47. doi: 10.1084/jem.178.1.27. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Gillis S., Smith K. A. Long term culture of tumour-specific cytotoxic T cells. Nature. 1977 Jul 14;268(5616):154–156. doi: 10.1038/268154a0. [DOI] [PubMed] [Google Scholar]
  5. Harding C. V., Kihlberg J., Elofsson M., Magnusson G., Unanue E. R. Glycopeptides bind MHC molecules and elicit specific T cell responses. J Immunol. 1993 Sep 1;151(5):2419–2425. [PubMed] [Google Scholar]
  6. Harding C. V., Roof R. W., Allen P. M., Unanue E. R. Effects of pH and polysaccharides on peptide binding to class II major histocompatibility complex molecules. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2740–2744. doi: 10.1073/pnas.88.7.2740. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Holmdahl R., Andersson M., Goldschmidt T. J., Gustafsson K., Jansson L., Mo J. A. Type II collagen autoimmunity in animals and provocations leading to arthritis. Immunol Rev. 1990 Dec;118:193–232. doi: 10.1111/j.1600-065x.1990.tb00817.x. [DOI] [PubMed] [Google Scholar]
  8. Holmdahl R., Karlsson M. Rapid method to determine structural polymorphism of rat major histocompatibility complex class II genes. Transplant Proc. 1993 Oct;25(5):2770–2770. [PubMed] [Google Scholar]
  9. Holmdahl R., Klareskog L., Andersson M., Hansen C. High antibody response to autologous type II collagen is restricted to H-2q. Immunogenetics. 1986;24(2):84–89. doi: 10.1007/BF00373114. [DOI] [PubMed] [Google Scholar]
  10. Ishioka G. Y., Lamont A. G., Thomson D., Bulbow N., Gaeta F. C., Sette A., Grey H. M. MHC interaction and T cell recognition of carbohydrates and glycopeptides. J Immunol. 1992 Apr 15;148(8):2446–2451. [PubMed] [Google Scholar]
  11. Michaëlsson E., Andersson M., Engström A., Holmdahl R. Identification of an immunodominant type-II collagen peptide recognized by T cells in H-2q mice: self tolerance at the level of determinant selection. Eur J Immunol. 1992 Jul;22(7):1819–1825. doi: 10.1002/eji.1830220722. [DOI] [PubMed] [Google Scholar]
  12. Monson J. M., Friedman J., McCarthy B. J. DNA sequence analysis of a mouse pro alpha 1 (I) procollagen gene: evidence for a mouse B1 element within the gene. Mol Cell Biol. 1982 Nov;2(11):1362–1371. doi: 10.1128/mcb.2.11.1362. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Myers L. K., Stuart J. M., Seyer J. M., Kang A. H. Identification of an immunosuppressive epitope of type II collagen that confers protection against collagen-induced arthritis. J Exp Med. 1989 Dec 1;170(6):1999–2010. doi: 10.1084/jem.170.6.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Schnieke A., Dziadek M., Bateman J., Mascara T., Harbers K., Gelinas R., Jaenisch R. Introduction of the human pro alpha 1(I) collagen gene into pro alpha 1(I)-deficient Mov-13 mouse cells leads to formation of functional mouse-human hybrid type I collagen. Proc Natl Acad Sci U S A. 1987 Feb;84(3):764–768. doi: 10.1073/pnas.84.3.764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Seyer J. M., Hasty K. A., Kang A. H. Covalent structure of collagen. Amino acid sequence of an arthritogenic cyanogen bromide peptide from type II collagen of bovine cartilage. Eur J Biochem. 1989 Apr 15;181(1):159–173. doi: 10.1111/j.1432-1033.1989.tb14707.x. [DOI] [PubMed] [Google Scholar]
  16. Smith B. D., Martin G. R., Miller E. J., Dorfman A., Swarm R. Nature of the collagen synthesized by a transplanted chondrosarcoma. Arch Biochem Biophys. 1975 Jan;166(1):181–186. doi: 10.1016/0003-9861(75)90378-1. [DOI] [PubMed] [Google Scholar]
  17. Spiro R. G. Studies on the renal glomerular basement membrane. Nature of the carbohydrate units and their attachment to the peptide portion. J Biol Chem. 1967 Apr 25;242(8):1923–1932. [PubMed] [Google Scholar]
  18. Trentham D. E., Dynesius-Trentham R. A., Orav E. J., Combitchi D., Lorenzo C., Sewell K. L., Hafler D. A., Weiner H. L. Effects of oral administration of type II collagen on rheumatoid arthritis. Science. 1993 Sep 24;261(5129):1727–1730. doi: 10.1126/science.8378772. [DOI] [PubMed] [Google Scholar]
  19. White J., Blackman M., Bill J., Kappler J., Marrack P., Gold D. P., Born W. Two better cell lines for making hybridomas expressing specific T cell receptors. J Immunol. 1989 Sep 15;143(6):1822–1825. [PubMed] [Google Scholar]
  20. Woodward H. D., Ringler N. J., Selvakumar R., Simet I. M., Bhavanandan V. P., Davidson E. A. Deglycosylation studies on tracheal mucin glycoproteins. Biochemistry. 1987 Aug 25;26(17):5315–5322. doi: 10.1021/bi00391a015. [DOI] [PubMed] [Google Scholar]
  21. Wooley P. H., Luthra H. S., Stuart J. M., David C. S. Type II collagen-induced arthritis in mice. I. Major histocompatibility complex (I region) linkage and antibody correlates. J Exp Med. 1981 Sep 1;154(3):688–700. doi: 10.1084/jem.154.3.688. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES