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Side-chain and backbone amide bond requirements for glycopeptide stimulation of T-cells obtained in a mouse model for rheumatoid arthritis

Holm, Lotta; Bockermann, Robert LU ; Wellner, Erik; Bäcklund, Johan LU ; Holmdahl, Rikard LU and Kihlberg, Jan (2006) In Bioorganic & Medicinal Chemistry 14(17). p.5921-5932
Abstract
Collagen induced arthritis (CIA) is the most studied animal model for rheumatoid arthritis and is associated with the MHC class II molecule A(q). T-cell recognition of a peptide from type II collagen, C11256-270, bound to A(q) is a requirement for development of CIA. Lysine 264 is the major T-cell recognition site of C11256-270 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... (More)
Collagen induced arthritis (CIA) is the most studied animal model for rheumatoid arthritis and is associated with the MHC class II molecule A(q). T-cell recognition of a peptide from type II collagen, C11256-270, bound to A(q) is a requirement for development of CIA. Lysine 264 is the major T-cell recognition site of C11256-270 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. (c) 2006 Elsevier Ltd. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
amide bond, rheumatoid arthritis, T-cell, glycopeptide, collagen, peptide mimetics, isostere
in
Bioorganic & Medicinal Chemistry
volume
14
issue
17
pages
5921 - 5932
publisher
Elsevier
external identifiers
  • pmid:16762555
  • wos:000239947500012
  • scopus:33746067093
ISSN
0968-0896
DOI
10.1016/j.bmc.2006.05.023
language
English
LU publication?
yes
id
c39bead9-91a3-448f-960a-c753aae04ef8 (old id 395315)
date added to LUP
2007-10-05 10:11:12
date last changed
2019-04-23 01:53:25
@article{c39bead9-91a3-448f-960a-c753aae04ef8,
  abstract     = {Collagen induced arthritis (CIA) is the most studied animal model for rheumatoid arthritis and is associated with the MHC class II molecule A(q). T-cell recognition of a peptide from type II collagen, C11256-270, bound to A(q) is a requirement for development of CIA. Lysine 264 is the major T-cell recognition site of C11256-270 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. (c) 2006 Elsevier Ltd. All rights reserved.},
  author       = {Holm, Lotta and Bockermann, Robert and Wellner, Erik and Bäcklund, Johan and Holmdahl, Rikard and Kihlberg, Jan},
  issn         = {0968-0896},
  keyword      = {amide bond,rheumatoid arthritis,T-cell,glycopeptide,collagen,peptide mimetics,isostere},
  language     = {eng},
  number       = {17},
  pages        = {5921--5932},
  publisher    = {Elsevier},
  series       = {Bioorganic & Medicinal Chemistry},
  title        = {Side-chain and backbone amide bond requirements for glycopeptide stimulation of T-cells obtained in a mouse model for rheumatoid arthritis},
  url          = {http://dx.doi.org/10.1016/j.bmc.2006.05.023},
  volume       = {14},
  year         = {2006},
}