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More MS news articles for September 2003

A novel rationale for inhibition of gelatinase B in multiple sclerosis: MMP-9 destroys alphaB-crystallin and generates a promiscuous T cell epitope

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12965253&dopt=Abstract

J Neuroimmunol. 2003 Aug;141(1-2):47-57
Starckx S, Van den Steen PE, Verbeek R, van Noort JM, Opdenakker G.
Rega Institute for Medical Research, Laboratory of Molecular Immunology, University of Leuven, Minderbroedersstraat 10, 3000, Leuven, Belgium

The small heat shock protein alphaB-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 alphaB-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 alphaB-crystallin in mice and rats were generated and largely left intact by MMP-9 processing.

The alphaB-crystallin peptide 1-16, generated as a remnant epitope, provoked a significant T cell response in alphaB-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 alphaB-crystallin, but their pathogenic role remains unclear.