Side-chain and backbone amide bond requirements for glycopeptide stimulation of T-cells obtained in a mouse model for rheumatoid arthritis
(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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https://lup.lub.lu.se/record/395315
- author
- Holm, Lotta ; Bockermann, Robert LU ; Wellner, Erik ; Bäcklund, Johan LU ; Holmdahl, Rikard LU and Kihlberg, Jan
- organization
- publishing date
- 2006
- 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
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Medical Inflammation Research (013212019)
- id
- c39bead9-91a3-448f-960a-c753aae04ef8 (old id 395315)
- date added to LUP
- 2016-04-01 11:55:01
- date last changed
- 2022-02-10 23:25:45
@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}},
keywords = {{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}},
doi = {{10.1016/j.bmc.2006.05.023}},
volume = {{14}},
year = {{2006}},
}