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000307665 1001_ $$aWang, Jian$$b0
000307665 245__ $$aEBV infection and HLA-DR15 jointly drive multiple sclerosis by myelin peptide presentation.
000307665 260__ $$a[Cambridge, Mass.]$$bCell Press$$c2026
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000307665 520__ $$aEpstein-Barr virus (EBV) is involved in causing and probably also in perpetuating multiple sclerosis (MS). Among several mechanisms of how EBV may contribute are transcriptome alterations, including changes of antigen processing and preferential presentation of both viral and self-antigens. Here, we report that EBV reprograms the transcriptome and immunopeptidome presented on the MS-associated human leukocyte antigen (HLA)-DR15 molecules of infected B cells. Identical myelin basic protein (MBP) peptides were found to be presented on both EBV-infected B cells and MS brain tissue but not primary B cells and thymic tissue. Peripheral memory and cerebrospinal fluid (CSF)-derived CD4+ T cells of HLA-DR15+ MS patients responded to MBP peptides, MBP(78-90) and/or MBP(83-90), and T cell clones raised with these peptides recognized all MBP peptides ending at amino acid MBP90 in MS brain tissue. Our study provides a new mechanistic link for how the environmental and genetic risk factors, EBV infection and HLA-DR15 haplotype, may contribute jointly to MS.
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000307665 650_7 $$2Other$$aB cells
000307665 650_7 $$2Other$$aEpstein-Barr virus
000307665 650_7 $$2Other$$aautoreactive CD4(+) T cells
000307665 650_7 $$2Other$$abrain tissue
000307665 650_7 $$2Other$$aimmunopeptidome
000307665 650_7 $$2Other$$amultiple sclerosis
000307665 650_7 $$2Other$$amyelin basic protein peptide
000307665 650_7 $$2Other$$athymic tissue
000307665 7001_ $$aQiu, Yuhan$$b1
000307665 7001_ $$aMarti, Zoe$$b2
000307665 7001_ $$aLi, Fengqi$$b3
000307665 7001_ $$aWacker, Marcel$$b4
000307665 7001_ $$aOldrati, Pietro$$b5
000307665 7001_ $$0P:(DE-He78)c6de4d8f2028af485dd5838bebdcb3e1$$aMühlenbruch, Lena$$b6
000307665 7001_ $$aJin, Linlin$$b7
000307665 7001_ $$aZhang, Hongxia$$b8
000307665 7001_ $$aXu, Wen$$b9
000307665 7001_ $$aLi, Tingting$$b10
000307665 7001_ $$aRoschitzki, Bernd$$b11
000307665 7001_ $$aFaigle, Wolfgang$$b12
000307665 7001_ $$aLiu, Yingjun$$b13
000307665 7001_ $$aNguyen, Julie T$$b14
000307665 7001_ $$aLee, Jar-How$$b15
000307665 7001_ $$aHaunerdinger, Veronika$$b16
000307665 7001_ $$aHauri-Hohl, Mathias$$b17
000307665 7001_ $$aMomburg, Frank$$b18
000307665 7001_ $$0P:(DE-He78)f01eee7fbf54dc1fe47b67c4eff9fdec$$aBauer, Jens$$b19$$udkfz
000307665 7001_ $$0P:(DE-He78)58a4f09f3edfdce451d520a5be7979fc$$aRammensee, Hans-Georg$$b20
000307665 7001_ $$aSospedra, Mireia$$b21
000307665 7001_ $$aMagliozzi, Roberta$$b22
000307665 7001_ $$aReynolds, Richard$$b23
000307665 7001_ $$0P:(DE-He78)aa8b428f7b1df6694113a5a7d3c4832a$$aWalz, Juliane$$b24$$udkfz
000307665 7001_ $$aMartin, Roland$$b25
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