Generation of glycosylated remnant epitopes from human collagen type II by gelatinase B

P. E. Van Den Steen, P. Proost, David Brand, Andrew Kang, J. Van Damme, G. Opdenakker

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Gelatinase B/matrix metalloproteinase-9 (MMP-9) is an inflammatory mediator and effector. Considerable amounts of gelatinase B are released by neutrophils in the synovial cavity of patients with rheumatoid arthritis, and gelatinase B-deficient mice are resistant against antibody-induced arthritis. Native human collagen type II is susceptible to cleavage by various collagenases (MMP-1, MMP-8, and MMP-13), which cleave at a single position in the triple helix. Although the triple-helical structure may persist after this single cleavage, we show that gelatinase B degrades the resulting fragments into small remnant peptides. These were identified by mass spectrometry and Edman degradation. Localization of 31 cleavage sites shows that the immunodominant epitopes remain intact after cleavage and may become available, processed as antigens and presented in MHC-II molecules. Furthermore, most post-translational modifications were identified on the fragments, including nine glycosylation sites. In particular, it is shown for the first time by structural analysis that in natural human collagen II, lysines in the main immunodominant epitope are modified by partial hydroxylation and partial glycosylation. Determination of T-cell reactivity against such fragments indicates that, besides the two known main immunodominant epitopes, other glyco-epitopes may be present in collagen II. This reinforces the role of glycopeptide antigens in autoimmunity.

Original languageEnglish (US)
Pages (from-to)10809-10816
Number of pages8
JournalBiochemistry
Volume43
Issue number33
DOIs
StatePublished - Aug 24 2004

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Collagen Type II
Matrix Metalloproteinase 9
Epitopes
Immunodominant Epitopes
Matrix Metalloproteinases
Glycosylation
Collagen
Antigens
Hydroxylation
T-cells
Glycopeptides
Collagenases
Post Translational Protein Processing
Autoimmunity
Population Groups
Structural analysis
Lysine
Arthritis
Mass spectrometry
Mass Spectrometry

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Generation of glycosylated remnant epitopes from human collagen type II by gelatinase B. / Van Den Steen, P. E.; Proost, P.; Brand, David; Kang, Andrew; Van Damme, J.; Opdenakker, G.

In: Biochemistry, Vol. 43, No. 33, 24.08.2004, p. 10809-10816.

Research output: Contribution to journalArticle

Van Den Steen, PE, Proost, P, Brand, D, Kang, A, Van Damme, J & Opdenakker, G 2004, 'Generation of glycosylated remnant epitopes from human collagen type II by gelatinase B', Biochemistry, vol. 43, no. 33, pp. 10809-10816. https://doi.org/10.1021/bi0493665
Van Den Steen, P. E. ; Proost, P. ; Brand, David ; Kang, Andrew ; Van Damme, J. ; Opdenakker, G. / Generation of glycosylated remnant epitopes from human collagen type II by gelatinase B. In: Biochemistry. 2004 ; Vol. 43, No. 33. pp. 10809-10816.
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