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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
23
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pubmed:dateCreated |
2007-11-8
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pubmed:abstractText |
T cells obtained in a mouse model for rheumatoid arthritis are activated by a glycopeptide fragment from rat type II collagen (CII) bound to the class II major histocompatibility complex Aq molecule. We report a comparative model of Aq in complex with the glycopeptide CII260-267. This model was used in a structure-based design approach where the amide bond between Ala261 and Gly262 in the glycopeptide was selected for replacement with psi[COCH2], psi[CH2NH2+], and psi[(E)-CH=CH] isosteres. Ala-Gly isostere building blocks were then synthesized and introduced in CII260-267 and CII259-273 glycopeptides. The modified glycopeptides were evaluated for binding to the Aq molecule, and the results were interpreted in view of the Aq/glycopeptide model. Moreover, recognition by a panel of T-cell hybridomas revealed high sensitivity for the backbone modifications. These studies contribute to the understanding of the interactions in the ternary Aq/glycopeptide/T-cell receptor complexes that activate T cells in autoimmune arthritis and suggest possibilities for new vaccination approaches.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0022-2623
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
50
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5627-43
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pubmed:meshHeading |
pubmed-meshheading:17944452-Alanine,
pubmed-meshheading:17944452-Animals,
pubmed-meshheading:17944452-Antigen-Presenting Cells,
pubmed-meshheading:17944452-Arthritis, Experimental,
pubmed-meshheading:17944452-Binding, Competitive,
pubmed-meshheading:17944452-Coculture Techniques,
pubmed-meshheading:17944452-Collagen Type II,
pubmed-meshheading:17944452-Glycine,
pubmed-meshheading:17944452-Glycopeptides,
pubmed-meshheading:17944452-Histocompatibility Antigens Class II,
pubmed-meshheading:17944452-Hybridomas,
pubmed-meshheading:17944452-Interleukin-2,
pubmed-meshheading:17944452-Mice,
pubmed-meshheading:17944452-Models, Molecular,
pubmed-meshheading:17944452-Molecular Structure,
pubmed-meshheading:17944452-Peptide Fragments,
pubmed-meshheading:17944452-Protein Binding,
pubmed-meshheading:17944452-Rats,
pubmed-meshheading:17944452-Receptors, Antigen, T-Cell,
pubmed-meshheading:17944452-Spleen,
pubmed-meshheading:17944452-Stereoisomerism,
pubmed-meshheading:17944452-Structure-Activity Relationship,
pubmed-meshheading:17944452-T-Lymphocytes
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pubmed:year |
2007
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pubmed:articleTitle |
Probing molecular interactions within class II MHC Aq/glycopeptide/T-cell receptor complexes associated with collagen-induced arthritis.
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pubmed:affiliation |
Department of Chemistry, Umeå University, SE-901 87 Umeå, Sweden.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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