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LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00005453naa a2200517 4500
001oai:DiVA.org:uu-484551
003SwePub
008220914s2022 | |||||||||||000 ||eng|
009oai:prod.swepub.kib.ki.se:148641273
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4845512 URI
0247 a https://doi.org/10.1136/annrheumdis-2021-2205002 DOI
0247 a http://kipublications.ki.se/Default.aspx?queryparsed=id:1486412732 URI
040 a (SwePub)uud (SwePub)ki
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Ge, Changrongu Karolinska Institutet4 aut
2451 0a Key interactions in the trimolecular complex consisting of the rheumatoid arthritis-associated DRB1*04:01 molecule, the major glycosylated collagen II peptide and the T-cell receptor
264 c 2022-01-13
264 1b BMJ Publishing Group Ltd,c 2022
338 a electronic2 rdacarrier
520 a Objectives Rheumatoid arthritis (RA) is an autoimmune disease strongly associated with the major histocompatibility complex (MHC) class II allele DRB1*04:01, which encodes a protein that binds self-peptides for presentation to T cells. This study characterises the autoantigen-presenting function of DRB1*04:01 (HLA-DRA*01:01/HLA-DRB1*04:01) at a molecular level for prototypic T-cell determinants, focusing on a post-translationally modified collagen type II (Col2)-derived peptide.Methods The crystal structures of DRB1*04:01 molecules in complex with the peptides HSP70(289-306), citrullinated CILP982-996 and galactosylated Col2(259-273) were determined on cocrystallisation. T cells specific for Col2(259-273) were investigated in peripheral blood mononuclear cells from patients with DRB1*04:01-positive RA by cytofluorometric detection of the activation marker CD154 on peptide stimulation and binding of fluorescent DRB1*0401/Col2(259-273) tetramer complexes. The cDNAs encoding the T-cell receptor (TCR) alpha-chains and beta-chains were cloned from single-cell sorted tetramer-positive T cells and transferred via a lentiviral vector into TCR-deficient Jurkat 76 cells.Results The crystal structures identified peptide binding to DRB1*04:01 and potential side chain exposure to T cells. The main TCR recognition sites in Col2(259-273) were lysine residues that can be galactosylated. RA T-cell responses to DRB1*04:01-presented Col2(259-273) were dependent on peptide galactosylation at lysine 264. Dynamic molecular modelling of a functionally characterised Col2(259-273)-specific TCR complexed with DRB1*04:01/Col2(259-273) provided evidence for differential allosteric T-cell recognition of glycosylated lysine 264.Conclusions The MHC-peptide-TCR interactions elucidated in our study provide new molecular insights into recognition of a post-translationally modified RA T-cell determinant with a known dominant role in arthritogenic and tolerogenic responses in murine Col2-induced arthritis.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Immunologi inom det medicinska området0 (SwePub)301102 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Immunology in the medical area0 (SwePub)301102 hsv//eng
653 a rheumatoid arthritis
653 a autoimmunity
653 a T-lymphocyte subsets
7001 a Weisse, Sylviau Fraunhofer Inst Translat Med & Pharmacol ITMP, Frankfurt, Germany4 aut
7001 a Xu, Bingzeu Karolinska Inst, Sect Med Inflammat Res, Dept Med Biochem & Biophys, Stockholm, Sweden4 aut
7001 a Dobritzsch, Doreen,d 1972-u Uppsala universitet,Biokemi4 aut0 (Swepub:uu)dordo526
7001 a Viljanen, Johan V.u Uppsala universitet,Organisk kemi4 aut0 (Swepub:uu)johvi609
7001 a Kihlberg, Janu Uppsala universitet,Organisk kemi4 aut0 (Swepub:uu)janki643
7001 a Do, Nhu-Nguyenu Karolinska Inst, Sect Med Inflammat Res, Dept Med Biochem & Biophys, Stockholm, Sweden.;Fraunhofer Inst Translat Med & Pharmacol ITMP, Frankfurt, Germany4 aut
7001 a Schneider, Nadineu Fraunhofer Inst Translat Med & Pharmacol ITMP, Frankfurt, Germany4 aut
7001 a Lanig, Haraldu Friedrich Alexander Univ Erlangen Nurnberg, Cent Inst Sci Comp ZISC, Erlangen, Germany.;Friedrich Alexander Univ Erlangen Nurnberg, Erlangen Natl High Performance Comp Ctr, Erlangen, Germany4 aut
7001 a Holmdahl, Rikardu Karolinska Institutet4 aut
7001 a Burkhardt, Haraldu Fraunhofer Inst Translat Med & Pharmacol ITMP, Frankfurt, Germany.;Fraunhofer Cluster Excellence Immune Mediated Dis, Frankfurt, Germany.;Goethe Univ, Univ Hosp Frankfurt, Div Rheumatol, Frankfurt, Germany4 aut
7102 a Karolinska Institutetb Fraunhofer Inst Translat Med & Pharmacol ITMP, Frankfurt, Germany4 org
7730 t Annals of the Rheumatic Diseasesd : BMJ Publishing Group Ltdg 81:4, s. 480-489q 81:4<480-489x 0003-4967x 1468-2060
8564 u https://doi.org/10.1136/annrheumdis-2021-220500y Fulltext
8564 u https://uu.diva-portal.org/smash/get/diva2:1695752/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
8564 u https://ard.bmj.com/content/annrheumdis/early/2022/01/12/annrheumdis-2021-220500.full.pdf
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-484551
8564 8u https://doi.org/10.1136/annrheumdis-2021-220500
8564 8u http://kipublications.ki.se/Default.aspx?queryparsed=id:148641273

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