{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T08:09:54Z","timestamp":1774512594721,"version":"3.50.1"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2008,8,29]],"date-time":"2008-08-29T00:00:00Z","timestamp":1219968000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2008,8,29]],"date-time":"2008-08-29T00:00:00Z","timestamp":1219968000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Introduction<\/jats:title>\n                        <jats:p>Ankylosing spondylitis (AS) is a severe, chronic inflammatory arthritis, with a strong association to the human major histocompatibilty complex (MHC) class I allele human leucocyte antigen (HLA) B27. Disulfide-linked HLA-B27 heavy-chain homodimers have been implicated as novel structures involved in the aetiology of AS. We have studied the formation of HLA-B27 heavy-chain homodimers in human dendritic cells, which are key antigen-presenting cells and regulators of mammalian immune responses.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Method<\/jats:title>\n                        <jats:p>Both an <jats:italic>in vitro<\/jats:italic> dendritic-like cell line and monocyte-derived dendritic cells from peripheral blood were studied. The KG-1 dendritic-like cell line was transfected with HLA-B27 cDNA constructs, and the cellular distribution, intracellular assembly and ability of HLA-B27 to form heavy-chain homodimers was compared with human monocyte-derived dendritic cells after stimulation with bacterial lipopolysaccharide (LPS).<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>Immature KG-1 cells expressing HLA-B27 display an intracellular source of MHC class I heavy-chain homodimers partially overlapping with the Golgi bodies, but not the endoplasmic reticulum, which is lost at cell maturation with phorbyl-12-myristate-13-acetate (PMA) and ionomycin. Significantly, the formation of HLA-B27 homodimers in transfected KG-1 cells is induced by maturation, with a transient induction also seen in LPS-stimulated human monocyte-derived dendritic cells expressing HLA-B27. The weak association of wildtype HLA-B*2705 with the transporter associated with antigen processing could also be enhanced by mutation of residues at position 114 and 116 in the peptide-binding groove to those present in the HLA-B*2706 allele.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusion<\/jats:title>\n                        <jats:p>We have demonstrated that HLA-B27 heavy-chain homodimer formation can be induced by dendritic cell activation, implying that these novel structures may not be displayed to the immune system at all times. Our data suggests that the behaviour of HLA-B27 on dendritic cells may be important in the study of inflammatory arthritis.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/ar2492","type":"journal-article","created":{"date-parts":[[2008,9,9]],"date-time":"2008-09-09T18:10:26Z","timestamp":1220983826000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Induction of HLA-B27 heavy chain homodimer formation after activation in dendritic cells"],"prefix":"10.1186","volume":"10","author":[{"given":"Susana G","family":"Santos","sequence":"first","affiliation":[]},{"given":"Sarah","family":"Lynch","sequence":"additional","affiliation":[]},{"given":"Elaine C","family":"Campbell","sequence":"additional","affiliation":[]},{"given":"Antony N","family":"Antoniou","sequence":"additional","affiliation":[]},{"given":"Simon J","family":"Powis","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2008,8,29]]},"reference":[{"key":"2341_CR1","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1034\/j.1399-0039.2002.600301.x","volume":"60","author":"M Ramos","year":"2002","unstructured":"Ramos M, Lopez de Castro JA: HLA-B27 and the pathogenesis of spondyloarthritis. Tissue Antigens. 2002, 60: 191-205. 10.1034\/j.1399-0039.2002.600301.x.","journal-title":"Tissue Antigens"},{"key":"2341_CR2","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.4049\/jimmunol.170.2.1099","volume":"170","author":"E May","year":"2003","unstructured":"May E, Dorris ML, Satumtira N, Iqbal I, Rehman MI, Lightfoot E, Taurog JD: CD8 alpha beta T cells are not essential to the pathogenesis of arthritis or colitis in HLA-B27 transgenic rats. J Immunol. 2003, 170: 1099-1105.","journal-title":"J Immunol"},{"key":"2341_CR3","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1016\/j.berh.2006.03.001","volume":"20","author":"JA Smith","year":"2006","unstructured":"Smith JA, Marker-Hermann E, Colbert RA: Pathogenesis of ankylosing spondylitis: current concepts. Best Pract Res Clin Rheumatol. 2006, 20: 571-591. 10.1016\/j.berh.2006.03.001.","journal-title":"Best Pract Res Clin Rheumatol"},{"key":"2341_CR4","doi-asserted-by":"publisher","first-page":"41","DOI":"10.2174\/1566524043479275","volume":"4","author":"MA Penttinen","year":"2004","unstructured":"Penttinen MA, Ekman P, Granfors K: Non-antigen presenting effects of HLA-B27. Curr Mol Med. 2004, 4: 41-49. 10.2174\/1566524043479275.","journal-title":"Curr Mol Med"},{"key":"2341_CR5","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1002\/art.22295","volume":"56","author":"MJ Turner","year":"2007","unstructured":"Turner MJ, Delay ML, Bai S, Klenk E, Colbert RA: HLA-B27 up-regulation causes accumulation of misfolded heavy chains and correlates with the magnitude of the unfolded protein response in transgenic rats: implications for the pathogenesis of spondylarthritis-like disease. Arthritis Rheum. 2007, 56: 215-223. 10.1002\/art.22295.","journal-title":"Arthritis Rheum"},{"key":"2341_CR6","doi-asserted-by":"publisher","first-page":"2972","DOI":"10.1002\/art.10605","volume":"46","author":"S Kollnberger","year":"2002","unstructured":"Kollnberger S, Bird L, Sun MY, Retiere C, Braud VM, McMichael A, Bowness P: Cell-surface expression and immune receptor recognition of HLA-B27 homodimers. Arthritis Rheum. 2002, 46: 2972-2982. 10.1002\/art.10605.","journal-title":"Arthritis Rheum"},{"key":"2341_CR7","doi-asserted-by":"crossref","first-page":"5045","DOI":"10.4049\/jimmunol.162.9.5045","volume":"162","author":"RL Allen","year":"1999","unstructured":"Allen RL, O'Callaghan CA, McMichael AJ, Bowness P: Cutting edge: HLA-B27 can form a novel beta 2-microglobulin-free heavy chain homodimer structure. J Immunol. 1999, 162: 5045-5048.","journal-title":"J Immunol"},{"key":"2341_CR8","doi-asserted-by":"publisher","first-page":"8895","DOI":"10.1074\/jbc.M311757200","volume":"279","author":"AN Antoniou","year":"2004","unstructured":"Antoniou AN, Ford S, Taurog JD, Butcher GW, Powis SJ: Formation of HLA-B27 homodimers and their relationship to assembly kinetics. J Biol Chem. 2004, 279: 8895-8902. 10.1074\/jbc.M311757200.","journal-title":"J Biol Chem"},{"key":"2341_CR9","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1002\/eji.200323678","volume":"33","author":"LA Bird","year":"2003","unstructured":"Bird LA, Peh CA, Kollnberger S, Elliott T, McMichael AJ, Bowness P: Lymphoblastoid cells express HLA-B27 homodimers both intracellularly and at the cell surface following endosomal recycling. Eur J Immunol. 2003, 33: 748-759. 10.1002\/eji.200323678.","journal-title":"Eur J Immunol"},{"key":"2341_CR10","doi-asserted-by":"publisher","first-page":"5110","DOI":"10.4049\/jimmunol.172.8.5110","volume":"172","author":"TM Tran","year":"2004","unstructured":"Tran TM, Satumtira N, Dorris ML, May E, Wang A, Furuta E, Taurog JD: HLA-B27 in transgenic rats forms disulfide-linked heavy chain oligomers and multimers that bind to the chaperone BiP. J Immunol. 2004, 172: 5110-5119.","journal-title":"J Immunol"},{"key":"2341_CR11","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1002\/eji.200635997","volume":"37","author":"S Kollnberger","year":"2007","unstructured":"Kollnberger S, Chan A, Sun MY, Chen LY, Wright C, di Gleria K, McMichael A, Bowness P: Interaction of HLA-B27 homodimers with KIR3DL1 and KIR3DL2, unlike HLA-B27 heterotrimers, is independent of the sequence of bound peptide. Eur J Immunol. 2007, 37: 1313-1322. 10.1002\/eji.200635997.","journal-title":"Eur J Immunol"},{"key":"2341_CR12","doi-asserted-by":"publisher","first-page":"3586","DOI":"10.1002\/art.21395","volume":"52","author":"AT Chan","year":"2005","unstructured":"Chan AT, Kollnberger SD, Wedderburn LR, Bowness P: Expansion and enhanced survival of natural killer cells expressing the killer immunoglobulin-like receptor KIR3DL2 in spondylarthritis. Arthritis Rheum. 2005, 52: 3586-3595. 10.1002\/art.21395.","journal-title":"Arthritis Rheum"},{"key":"2341_CR13","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1111\/j.1600-065X.2006.00450.x","volume":"214","author":"L Moretta","year":"2006","unstructured":"Moretta L, Ferlazzo G, Bottino C, Vitale M, Pende D, Mingari MC, Moretta A: Effector and regulatory events during natural killer-dendritic cell interactions. Immunol Rev. 2006, 214: 219-228. 10.1111\/j.1600-065X.2006.00450.x.","journal-title":"Immunol Rev"},{"key":"2341_CR14","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1111\/j.1600-065X.2007.00551.x","volume":"219","author":"H Ueno","year":"2007","unstructured":"Ueno H, Klechevsky E, Morita R, Aspord C, Cao T, Matsui T, Di Pucchio T, Connolly J, Fay JW, Pascual V, Palucka AK, Banchereau J: Dendritic cell subsets in health and disease. Immunol Rev. 2007, 219: 118-142. 10.1111\/j.1600-065X.2007.00551.x.","journal-title":"Immunol Rev"},{"key":"2341_CR15","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.1002\/art.22572","volume":"56","author":"C Hacquard-Bouder","year":"2007","unstructured":"Hacquard-Bouder C, Chimenti MS, Giquel B, Donnadieu E, Fert I, Schmitt A, Andre C, Breban M: Alteration of antigen-independent immunologic synapse formation between dendritic cells from HLA-B27-transgenic rats and CD4+ T cells: selective impairment of costimulatory molecule engagement by mature HLA-B27. Arthritis Rheum. 2007, 56: 1478-1489. 10.1002\/art.22572.","journal-title":"Arthritis Rheum"},{"key":"2341_CR16","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1099\/0022-1317-73-3-653","volume":"73","author":"T Hanke","year":"1992","unstructured":"Hanke T, Szawlowski P, Randall RE: Construction of solid matrix-antibody-antigen complexes containing simian immunodeficiency virus p27 using tag-specific monoclonal antibody and tag-linked antigen. J Gen Virol. 1992, 73: 653-660. 10.1099\/0022-1317-73-3-653.","journal-title":"J Gen Virol"},{"key":"2341_CR17","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1016\/1074-7613(94)90091-4","volume":"1","author":"PM van Endert","year":"1994","unstructured":"van Endert PM, Tampe R, Meyer TH, Tisch R, Bach JF, McDevitt HO: A sequential model for peptide binding and transport by the transporters associated with antigen processing. Immunity. 1994, 1: 491-500. 10.1016\/1074-7613(94)90091-4.","journal-title":"Immunity"},{"key":"2341_CR18","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1046\/j.1365-2567.2002.01415.x","volume":"106","author":"AN Antoniou","year":"2002","unstructured":"Antoniou AN, Ford S, Pilley ES, Blake N, Powis SJ: Interactions formed by individually expressed TAP1 and TAP2 polypeptide subunits. Immunology. 2002, 106: 182-189. 10.1046\/j.1365-2567.2002.01415.x.","journal-title":"Immunology"},{"key":"2341_CR19","doi-asserted-by":"publisher","first-page":"4178","DOI":"10.4049\/jimmunol.170.8.4178","volume":"170","author":"AL Ackerman","year":"2003","unstructured":"Ackerman AL, Cresswell P: Regulation of MHC class I transport in human dendritic cells and the dendritic-like cell line KG-1. J Immunol. 2003, 170: 4178-4188.","journal-title":"J Immunol"},{"key":"2341_CR20","doi-asserted-by":"publisher","first-page":"17587","DOI":"10.1074\/jbc.M702212200","volume":"282","author":"SG Santos","year":"2007","unstructured":"Santos SG, Campbell EC, Lynch S, Wong V, Antoniou AN, Powis SJ: Major histocompatibility complex class I-ERp57-tapasin interactions within the peptide-loading complex. J Biol Chem. 2007, 282: 17587-17593. 10.1074\/jbc.M702212200.","journal-title":"J Biol Chem"},{"key":"2341_CR21","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1002\/art.23164","volume":"58","author":"B Galocha","year":"2008","unstructured":"Galocha B, de Castro JA: Folding of HLA-B27 subtypes is determined by the global effect of polymorphic residues and shows incomplete correspondence to ankylosing spondylitis. Arthritis Rheum. 2008, 58: 401-412. 10.1002\/art.23164.","journal-title":"Arthritis Rheum"},{"key":"2341_CR22","doi-asserted-by":"publisher","first-page":"3982","DOI":"10.1073\/pnas.071477498","volume":"98","author":"PA MacAry","year":"2001","unstructured":"MacAry PA, Lindsay M, Scott MA, Craig JI, Luzio JP, Lehner PJ: Mobilization of MHC class I molecules from late endosomes to the cell surface following activation of CD34-derived human Langerhans cells. Proc Natl Acad Sci USA. 2001, 98: 3982-3987. 10.1073\/pnas.071477498.","journal-title":"Proc Natl Acad Sci USA"},{"key":"2341_CR23","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1016\/S1074-7613(02)00304-7","volume":"16","author":"AP Williams","year":"2002","unstructured":"Williams AP, Peh CA, Purcell AW, McCluskey J, Elliott T: Optimization of the MHC class I peptide cargo is dependent on tapasin. Immunity. 2002, 16: 509-520. 10.1016\/S1074-7613(02)00304-7.","journal-title":"Immunity"},{"key":"2341_CR24","doi-asserted-by":"publisher","first-page":"961","DOI":"10.4049\/jimmunol.170.2.961","volume":"170","author":"B Park","year":"2003","unstructured":"Park B, Lee S, Kim E, Ahn K: A single polymorphic residue within the peptide-binding cleft of MHC class I molecules determines spectrum of tapasin dependence. J Immunol. 2003, 170: 961-968.","journal-title":"J Immunol"},{"key":"2341_CR25","doi-asserted-by":"publisher","first-page":"6673","DOI":"10.4049\/jimmunol.176.11.6673","volume":"176","author":"DR Fooksman","year":"2006","unstructured":"Fooksman DR, Gronvall GK, Tang Q, Edidin M: Clustering class I MHC modulates sensitivity of T cell recognition. J Immunol. 2006, 176: 6673-6680.","journal-title":"J Immunol"},{"key":"2341_CR26","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1111\/j.1600-065X.1999.tb01317.x","volume":"169","author":"JD Taurog","year":"1999","unstructured":"Taurog JD, Maika SD, Satumtira N, Dorris ML, McLean IL, Yanagisawa H, Sayad A, Stagg AJ, Fox GM, Le O'Brien A, Rehman M, Zhou M, Weiner AL, Splawski JB, Richardson JA, Hammer RE: Inflammatory disease in HLA-B27 transgenic rats. Immunol Rev. 1999, 169: 209-223. 10.1111\/j.1600-065X.1999.tb01317.x.","journal-title":"Immunol Rev"},{"key":"2341_CR27","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1189\/jlb.0603250","volume":"75","author":"H Kobayashi","year":"2004","unstructured":"Kobayashi H, Miura S, Nagata H, Tsuzuki Y, Hokari R, Ogino T, Watanabe C, Azuma T, Ishii H: In situ demonstration of dendritic cell migration from rat intestine to mesenteric lymph nodes: relationships to maturation and role of chemokines. Journal of Leukocyte Biology. 2004, 75: 434-442. 10.1189\/jlb.0603250.","journal-title":"Journal of Leukocyte Biology"},{"key":"2341_CR28","doi-asserted-by":"publisher","first-page":"53062","DOI":"10.1074\/jbc.M408794200","volume":"279","author":"SG Santos","year":"2004","unstructured":"Santos SG, Powis SJ, Arosa FA: Misfolding of major histocompatibility complex class I molecules in activated T cells allows cis-interactions with receptors and signaling molecules and is associated with tyrosine phosphorylation. J Biol Chem. 2004, 279: 53062-53070. 10.1074\/jbc.M408794200.","journal-title":"J Biol Chem"},{"key":"2341_CR29","doi-asserted-by":"publisher","first-page":"1258","DOI":"10.1016\/j.bbadis.2007.10.005","volume":"1772","author":"R Sharma","year":"2007","unstructured":"Sharma R, Vasishta RK, Sen RK, Luthra-Guptasarma M: Refolding of HLA-B27 heavy chains in the absence of beta2m yields stable high molecular weight (HMW) protein forms displaying native-like as well as non-native-like conformational features: implications for autoimmune disease. Biochim Biophys Acta. 2007, 1772: 1258-1269.","journal-title":"Biochim Biophys Acta"}],"container-title":["Arthritis Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/ar2492.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/ar2492\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/ar2492.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T10:33:20Z","timestamp":1728383600000},"score":1,"resource":{"primary":{"URL":"https:\/\/arthritis-research.biomedcentral.com\/articles\/10.1186\/ar2492"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,8,29]]},"references-count":29,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2008,8]]}},"alternative-id":["2341"],"URL":"https:\/\/doi.org\/10.1186\/ar2492","relation":{},"ISSN":["1478-6354"],"issn-type":[{"value":"1478-6354","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,8,29]]},"assertion":[{"value":"17 April 2008","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 July 2008","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 August 2008","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 August 2008","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"R100"}}