Title
A novel rationale for inhibition of gelatinase B in multiple sclerosis: MMP-9 destroys αB-crystallin and generates a promiscuous T cell epitope
Author
TNO Preventie en Gezondheid
Starckx, S.
van den Steen, P.E.
Verbeek, R.
van Noort, J.M.
Opdenakker, G.
Publication year
2003
Abstract
The small heat shock protein αB-crystallin is considered as a candidate autoantigen in multiple sclerosis (MS) lesions. Gelatinase B or matrix metalloproteinase (MMP)-9 is a proteinase establishing various disease-promoting feedback loops in autoimmune diseases. Human αB-crystallin was digested with natural gelatinase B and all cleavage sites were identified by a combined approach of mass spectrometry and peptide sequencing analysis. Previously identified immunodominant and cryptic epitopes of αB-crystallin in mice and rats were generated and largely left intact by MMP-9 processing. The αB-crystallin peptide 1-16, generated as a remnant epitope, provoked a significant T cell response in αB-crystallin knockout mice. None of the remnant peptides was encephalitogenic when injected intracerebrally into mice or induced MMP-9 in vitro. Gelatinase B is thus able to release T cell epitopes from intact αB-crystallin, but their pathogenic role remains unclear. © 2003 Elsevier B.V. All rights reserved. Chemicals/CAS: encephalitogenic protein, 29705-91-7; gelatinase B, 146480-36-6; alpha-Crystallin B Chain; Epitopes, T-Lymphocyte; Matrix Metalloproteinase 9, EC 3.4.24.35; Peptide Fragments; Recombinant Proteins
Subject
αB-crystallin
EAE
Gelatinase B
MMP-9
MS
Remnant T cell epitope
alpha b crystallin
autoantigen
encephalitogenic protein
epitope
gelatinase B
unclassified drug
amino acid sequence
article
autoimmune disease
controlled study
human
human cell
immune response
immune system
in vitro study
in vivo study
knockout mouse
mass spectrometry
mouse
multiple sclerosis
neuroimmunology
nonhuman
peptide analysis
priority journal
proteinase inhibition
rat
statistical significance
alpha-Crystallin B Chain
Amino Acid Sequence
Animals
Cell Line, Tumor
Epitopes, T-Lymphocyte
Humans
Hydrolysis
Injections, Intraventricular
Lymphocyte Activation
Matrix Metalloproteinase 9
Mice
Mice, Inbred C57BL
Mice, Knockout
Molecular Sequence Data
Multiple Sclerosis
Peptide Fragments
Rats
Rats, Inbred Lew
Recombinant Proteins
T-Lymphocytes
To reference this document use:
http://resolver.tudelft.nl/uuid:437f047a-0422-4c1a-95f7-65dbf9a9138d
DOI
https://doi.org/10.1016/s0165-5728(03)00217-0
TNO identifier
237211
ISSN
0165-5728
Source
Journal of Neuroimmunology, 141 (141), 47-57
Document type
article