Print Email Facebook Twitter A novel rationale for inhibition of gelatinase B in multiple sclerosis 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 184.108.40.206; Peptide Fragments; Recombinant Proteins Subject αB-crystallinEAEGelatinase BMMP-9MSRemnant T cell epitopealpha b crystallinautoantigenencephalitogenic proteinepitopegelatinase Bunclassified drugamino acid sequencearticleautoimmune diseasecontrolled studyhumanhuman cellimmune responseimmune systemin vitro studyin vivo studyknockout mousemass spectrometrymousemultiple sclerosisneuroimmunologynonhumanpeptide analysispriority journalproteinase inhibitionratstatistical significancealpha-Crystallin B ChainAmino Acid SequenceAnimalsCell Line, TumorEpitopes, T-LymphocyteHumansHydrolysisInjections, IntraventricularLymphocyte ActivationMatrix Metalloproteinase 9MiceMice, Inbred C57BLMice, KnockoutMolecular Sequence DataMultiple SclerosisPeptide FragmentsRatsRats, Inbred LewRecombinant ProteinsT-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 Files To receive the publication files, please send an e-mail request to TNO Library.