Antibody cross-reactivity between myelin oligodendrocyte glycoprotein and the milk protein butyrophilin in multiple sclerosis

J. Guggenmos, A. S. Schubart, S. Ogg, M. Andersson, T. Olsson, I. Mather, Christopher Linington

    Research output: Contribution to journalArticle

    77 Citations (Scopus)

    Abstract

    The etiology of multiple sclerosis (MS) is believed to involve environmental factors, but their identity and mode of action are unknown. In this study, we demonstrate that Ab specific for the extracellular Ig-like domain of myelin oligodendrocyte glycoprotein (MOG) cross-reacts with a homologous N-terminal domain of the bovine milk protein butyrophilin (BTN). Analysis of paired samples of MS sera and cerebrospinal fluid (CSF) identified a BTN-specific Ab response in the CNS that differed in its epitope specificity from that in the periphery. This effect was statistically significant for the Ab response to BTN76-100 (p = 0.0026), which cosequestered in the CSF compartment with Ab to the homologous MOG peptide MOG(76-100) in 34% of MS patients (n = 35). These observations suggested that intratheccal synthesis of Ab recognizing BTN peptide epitopes in the CNS was sustained by molecular mimicry with MOG. Formal evidence of molecular mimicry between the two proteins was obtained by analyzing MOG-specific autoantibodies immunopurified from MS sera. The MOG-specific Ab repertoire cross-reacts with multiple BTN peptide epitopes including a MOG/BTN76-100-specific component that occurred at a higher frequency in MS patients than in seropositive healthy controls, as well as responses to epitopes within MOG/BTN1-39 that occur at similar frequencies in both groups. The demonstration of molecular mimicry between MOG and BTN, along with sequestration of BTN-reactive AV in CSF suggests that exposure to this common dietary Ag may influence the composition and function of the MOG-specific autoimmune repertoire during the course of MS.

    Original languageEnglish
    Pages (from-to)661-668
    Number of pages7
    JournalThe Journal of Immunology
    Volume172
    Publication statusPublished - Jan 2004

    Keywords

    • EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS
    • B-CELL RESPONSES
    • T-CELL
    • MOLECULAR MIMICRY
    • BASIC-PROTEIN
    • ORAL TOLERANCE
    • MYELIN/OLIGODENDROCYTE GLYCOPROTEIN
    • EXTRACELLULAR DOMAIN
    • IMMUNE-RESPONSES
    • VIRAL PEPTIDE

    Cite this

    Guggenmos, J., Schubart, A. S., Ogg, S., Andersson, M., Olsson, T., Mather, I., & Linington, C. (2004). Antibody cross-reactivity between myelin oligodendrocyte glycoprotein and the milk protein butyrophilin in multiple sclerosis. The Journal of Immunology, 172, 661-668.

    Antibody cross-reactivity between myelin oligodendrocyte glycoprotein and the milk protein butyrophilin in multiple sclerosis. / Guggenmos, J.; Schubart, A. S.; Ogg, S.; Andersson, M.; Olsson, T.; Mather, I.; Linington, Christopher.

    In: The Journal of Immunology, Vol. 172, 01.2004, p. 661-668.

    Research output: Contribution to journalArticle

    Guggenmos, J, Schubart, AS, Ogg, S, Andersson, M, Olsson, T, Mather, I & Linington, C 2004, 'Antibody cross-reactivity between myelin oligodendrocyte glycoprotein and the milk protein butyrophilin in multiple sclerosis', The Journal of Immunology, vol. 172, pp. 661-668.
    Guggenmos, J. ; Schubart, A. S. ; Ogg, S. ; Andersson, M. ; Olsson, T. ; Mather, I. ; Linington, Christopher. / Antibody cross-reactivity between myelin oligodendrocyte glycoprotein and the milk protein butyrophilin in multiple sclerosis. In: The Journal of Immunology. 2004 ; Vol. 172. pp. 661-668.
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    abstract = "The etiology of multiple sclerosis (MS) is believed to involve environmental factors, but their identity and mode of action are unknown. In this study, we demonstrate that Ab specific for the extracellular Ig-like domain of myelin oligodendrocyte glycoprotein (MOG) cross-reacts with a homologous N-terminal domain of the bovine milk protein butyrophilin (BTN). Analysis of paired samples of MS sera and cerebrospinal fluid (CSF) identified a BTN-specific Ab response in the CNS that differed in its epitope specificity from that in the periphery. This effect was statistically significant for the Ab response to BTN76-100 (p = 0.0026), which cosequestered in the CSF compartment with Ab to the homologous MOG peptide MOG(76-100) in 34{\%} of MS patients (n = 35). These observations suggested that intratheccal synthesis of Ab recognizing BTN peptide epitopes in the CNS was sustained by molecular mimicry with MOG. Formal evidence of molecular mimicry between the two proteins was obtained by analyzing MOG-specific autoantibodies immunopurified from MS sera. The MOG-specific Ab repertoire cross-reacts with multiple BTN peptide epitopes including a MOG/BTN76-100-specific component that occurred at a higher frequency in MS patients than in seropositive healthy controls, as well as responses to epitopes within MOG/BTN1-39 that occur at similar frequencies in both groups. The demonstration of molecular mimicry between MOG and BTN, along with sequestration of BTN-reactive AV in CSF suggests that exposure to this common dietary Ag may influence the composition and function of the MOG-specific autoimmune repertoire during the course of MS.",
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    T1 - Antibody cross-reactivity between myelin oligodendrocyte glycoprotein and the milk protein butyrophilin in multiple sclerosis

    AU - Guggenmos, J.

    AU - Schubart, A. S.

    AU - Ogg, S.

    AU - Andersson, M.

    AU - Olsson, T.

    AU - Mather, I.

    AU - Linington, Christopher

    PY - 2004/1

    Y1 - 2004/1

    N2 - The etiology of multiple sclerosis (MS) is believed to involve environmental factors, but their identity and mode of action are unknown. In this study, we demonstrate that Ab specific for the extracellular Ig-like domain of myelin oligodendrocyte glycoprotein (MOG) cross-reacts with a homologous N-terminal domain of the bovine milk protein butyrophilin (BTN). Analysis of paired samples of MS sera and cerebrospinal fluid (CSF) identified a BTN-specific Ab response in the CNS that differed in its epitope specificity from that in the periphery. This effect was statistically significant for the Ab response to BTN76-100 (p = 0.0026), which cosequestered in the CSF compartment with Ab to the homologous MOG peptide MOG(76-100) in 34% of MS patients (n = 35). These observations suggested that intratheccal synthesis of Ab recognizing BTN peptide epitopes in the CNS was sustained by molecular mimicry with MOG. Formal evidence of molecular mimicry between the two proteins was obtained by analyzing MOG-specific autoantibodies immunopurified from MS sera. The MOG-specific Ab repertoire cross-reacts with multiple BTN peptide epitopes including a MOG/BTN76-100-specific component that occurred at a higher frequency in MS patients than in seropositive healthy controls, as well as responses to epitopes within MOG/BTN1-39 that occur at similar frequencies in both groups. The demonstration of molecular mimicry between MOG and BTN, along with sequestration of BTN-reactive AV in CSF suggests that exposure to this common dietary Ag may influence the composition and function of the MOG-specific autoimmune repertoire during the course of MS.

    AB - The etiology of multiple sclerosis (MS) is believed to involve environmental factors, but their identity and mode of action are unknown. In this study, we demonstrate that Ab specific for the extracellular Ig-like domain of myelin oligodendrocyte glycoprotein (MOG) cross-reacts with a homologous N-terminal domain of the bovine milk protein butyrophilin (BTN). Analysis of paired samples of MS sera and cerebrospinal fluid (CSF) identified a BTN-specific Ab response in the CNS that differed in its epitope specificity from that in the periphery. This effect was statistically significant for the Ab response to BTN76-100 (p = 0.0026), which cosequestered in the CSF compartment with Ab to the homologous MOG peptide MOG(76-100) in 34% of MS patients (n = 35). These observations suggested that intratheccal synthesis of Ab recognizing BTN peptide epitopes in the CNS was sustained by molecular mimicry with MOG. Formal evidence of molecular mimicry between the two proteins was obtained by analyzing MOG-specific autoantibodies immunopurified from MS sera. The MOG-specific Ab repertoire cross-reacts with multiple BTN peptide epitopes including a MOG/BTN76-100-specific component that occurred at a higher frequency in MS patients than in seropositive healthy controls, as well as responses to epitopes within MOG/BTN1-39 that occur at similar frequencies in both groups. The demonstration of molecular mimicry between MOG and BTN, along with sequestration of BTN-reactive AV in CSF suggests that exposure to this common dietary Ag may influence the composition and function of the MOG-specific autoimmune repertoire during the course of MS.

    KW - EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

    KW - B-CELL RESPONSES

    KW - T-CELL

    KW - MOLECULAR MIMICRY

    KW - BASIC-PROTEIN

    KW - ORAL TOLERANCE

    KW - MYELIN/OLIGODENDROCYTE GLYCOPROTEIN

    KW - EXTRACELLULAR DOMAIN

    KW - IMMUNE-RESPONSES

    KW - VIRAL PEPTIDE

    M3 - Article

    VL - 172

    SP - 661

    EP - 668

    JO - The Journal of Immunology

    JF - The Journal of Immunology

    SN - 0022-1767

    ER -