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

J Immunol. 2004 Jan 1;172(1):661-8. doi: 10.4049/jimmunol.172.1.661.


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 BTN(76-100) (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/BTN(76-100)-specific component that occurred at a higher frequency in MS patients than in seropositive healthy controls, as well as responses to epitopes within MOG/BTN(1-39) that occur at similar frequencies in both groups. The demonstration of molecular mimicry between MOG and BTN, along with sequestration of BTN-reactive Ab 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Animals
  • Autoantibodies / biosynthesis
  • Autoantibodies / blood
  • Butyrophilins
  • Cattle
  • Cross Reactions
  • Epitopes / immunology
  • Epitopes / metabolism
  • Female
  • Humans
  • Immune Sera / blood
  • Immune Sera / cerebrospinal fluid
  • Immune Sera / metabolism*
  • Male
  • Membrane Glycoproteins / immunology*
  • Membrane Glycoproteins / metabolism*
  • Middle Aged
  • Milk Proteins / immunology*
  • Milk Proteins / metabolism*
  • Molecular Mimicry / immunology
  • Molecular Sequence Data
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / cerebrospinal fluid
  • Multiple Sclerosis / immunology*
  • Myelin Proteins
  • Myelin-Associated Glycoprotein / immunology*
  • Myelin-Associated Glycoprotein / metabolism*
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism
  • Protein Structure, Tertiary


  • Autoantibodies
  • Butyrophilins
  • Epitopes
  • Immune Sera
  • MOG protein, human
  • Membrane Glycoproteins
  • Milk Proteins
  • Myelin Proteins
  • Myelin-Associated Glycoprotein
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments