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Autoreactive T Cells Recognize Unique MBP Peptides Naturally Presented by EBV-Infected B Cells and Multiple Sclerosis Brain Tissue

ABSTRACT: Epstein-Barr virus (EBV) is involved in causing and probably also perpetuating multiple sclerosis (MS). Among several mechanisms, how EBV may contribute, are transcriptome alterations including changes of antigen processing and preferential presentation of both viral and self-antigens. Here, we found that EBV reprograms the transcriptome and immunopeptidome presented on the MS-associated 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 tissues. Our study provides a new mechanistic link how the environmental and genetic risk factors, EBV infection and HLA-DR15 haplotype, may contribute jointly to MS.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell, Peripheral Blood Mononuclear Cell

DISEASE(S): Multiple Sclerosis

SUBMITTER: Bernd Roschitzki

LAB HEAD: Roland Martin

PROVIDER: PXD068927 | Pride | 2026-06-19

REPOSITORIES: Pride

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			Action	DRS
	20250605_003_S949311_MS4_MS.raw	Raw
	20250605_004_S949306_HD3_HD.raw	Raw
	20250605_008_S949310_MS3_MS.raw	Raw
	20250605_009_S949304_HD1_HD.raw	Raw
	20250605_014_S949308_MS1_MS.raw	Raw

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 Autoreactive T Cells Recognize Unique MBP Peptides Naturally Presented by EBV-Infected B Cells and Multiple Sclerosis Brain Tissue

Project description:Epstein-Barr virus (EBV) is involved in causing and probably also perpetuating multiple sclerosis (MS). Among several mechanisms, how EBV may contribute, are transcriptome alterations including changes of antigen processing and preferential presentation of both viral and self-antigens. Here, we found that EBV reprograms the transcriptome and immunopeptidome presented on the MS-associated 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 tissues. Our study provides a new mechanistic link how the environmental and genetic risk factors, EBV infection and HLA-DR15 haplotype, may contribute jointly to MS.

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HLA-DR15 Molecules Jointly Shape an Autoreactive T Cell Repertoire in Multiple Sclerosis

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