Design of glycopeptides used to investigate class II MHC binding and T-Cell responses associated with autoimmune arthritis

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Andersson, Ida E,1982-Umeå universitet,Kemiska institutionen (author)

Design of glycopeptides used to investigate class II MHC binding and T-Cell responses associated with autoimmune arthritis

Article/chapterEnglish2011

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2011-03-15
Public Library of Science,2011
electronicrdacarrier

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LIBRIS-ID:oai:DiVA.org:umu-41050
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-41050URI
https://doi.org/10.1371/journal.pone.0017881DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:122247909URI

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Language:English
Summary in:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

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Vid avhandlingens utgivning manuskript med annan titel: "Design of glycopeptide chemical probes used to investigate multiresponses associated with autoimmune arthritis"
The glycopeptide fragment CII259–273 from type II collagen (CII) binds to the murine Aq and human DR4 class II Major Histocompatibility Complex (MHC II) proteins, which are associated with development of murine collagen-induced arthritis (CIA) and rheumatoid arthritis (RA), respectively. It has been shown that CII259–273 can be used in therapeutic vaccination of CIA. This glycopeptide also elicits responses from T-cells obtained from RA patients, which indicates that it has an important role in RA as well. We now present a methodology for studies of (glyco)peptide-receptor interactions based on a combination of structure-based virtual screening, ligand-based statistical molecular design and biological evaluations. This methodology included the design of a CII259–273 glycopeptide library in which two anchor positions crucial for binding in pockets of Aq and DR4 were varied. Synthesis and biological evaluation of the designed glycopeptides provided novel structure-activity relationship (SAR) understanding of binding to Aq and DR4. Glycopeptides that retained high affinities for these MHC II proteins and induced strong responses in panels of T-cell hybridomas were also identified. An analysis of all the responses revealed groups of glycopeptides with different response patterns that are of high interest for vaccination studies in CIA. Moreover, the SAR understanding obtained in this study provides a platform for the design of second-generation glycopeptides with tuned MHC affinities and T-cell responses.

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NATURVETENSKAP Kemi hsv//swe
NATURAL SCIENCES Chemical Sciences hsv//eng

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Andersson, C David,1978-Umeå universitet,Kemiska institutionen(Swepub:umu)dadaon01 (author)
Batsalova, TsvetelinaMedicinal Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm (author)
Dzhambazov, BalikMedicinal Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm (author)
Holmdahl, RikardKarolinska Institutet (author)
Kihlberg, Jan,1957-Umeå universitet,Kemiska institutionen,AstraZeneca R&D Mölndal, Mölndal, Sweden(Swepub:umu)jaki0001 (author)
Linusson, Anna,1970-AstraZeneca R&D Mölndal, Mölndal(Swepub:umu)analin99 (author)
Umeå universitetKemiska institutionen (creator_code:org_t)

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In:PLOS ONE: Public Library of Science6:3, s. e17881-1932-6203

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By the university: Umeå University; Karolinska Institutet

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