Document Detail


Side-chain and backbone amide bond requirements for glycopeptide stimulation of T-cells obtained in a mouse model for rheumatoid arthritis.
MedLine Citation:
PMID:  16762555     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Collagen induced arthritis (CIA) is the most studied animal model for rheumatoid arthritis and is associated with the MHC class II molecule Aq. T-cell recognition of a peptide from type II collagen, CII256-270, bound to Aq is a requirement for development of CIA. Lysine 264 is the major T-cell recognition site of CII256-270 and CIA is in particular associated with recognition of lysine 264 after posttranslational hydroxylation and subsequent attachment of a beta-D-galactopyranosyl moiety. In this paper we have studied the structural requirements of collagenous glycopeptides required for T-cell stimulation, as an extension of earlier studies of the recognition of the galactose moiety. Synthesis and evaluation of alanine substituted glycopeptides revealed that there are T-cells that only recognise the galactosylated hydroxylysine 264, and no other amino acid side chains in the peptide. Other T-cells also require glutamic acid 266 as a T-cell contact point. Introduction of a methylene ether isostere instead of the amide bond between residues 260 and 261 allowed weaker recognition by some, but not all, of the T-cells. Altogether, these results allowed us to propose a model for glycopeptide recognition by the T-cells, where recognition from one or the other side of the galactose moiety could explain the different binding patterns of the T-cells.
Authors:
Lotta Holm; Robert Bockermann; Erik Wellner; Johan Bäcklund; Rikard Holmdahl; Jan Kihlberg
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-06-09
Journal Detail:
Title:  Bioorganic & medicinal chemistry     Volume:  14     ISSN:  0968-0896     ISO Abbreviation:  Bioorg. Med. Chem.     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-07-25     Completed Date:  2006-10-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9413298     Medline TA:  Bioorg Med Chem     Country:  England    
Other Details:
Languages:  eng     Pagination:  5921-32     Citation Subset:  IM    
Affiliation:
Organic Chemistry, Department of Chemistry, Umeå University, SE-901 87 Umeå, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arthritis, Rheumatoid / immunology*,  pathology
Disease Models, Animal
Glycopeptides / chemistry*,  immunology,  pharmacology*
Hybridomas / drug effects,  metabolism
Mice
Models, Molecular
Molecular Structure
Protein Binding
T-Lymphocytes / drug effects*,  immunology,  pathology
Chemical
Reg. No./Substance:
0/Glycopeptides

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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