T cells of multiple sclerosis patients target a common environmental peptide that causes encephalitis in mice.
Multiple sclerosis (MS) is a chronic autoimmune disease triggered by unknown environmental factors in genetically susceptible hosts. MS risk was linked to high rates of cow milk protein (CMP) consumption, reminiscent of a similar association in autoimmune diabetes. A recent rodent study showed that immune responses to the CMP, butyrophilin, can lead to encephalitis through antigenic mimicry with myelin oligodendrocyte glycoprotein. In this study, we show abnormal T cell immunity to several other CMPs in MS patients comparable to that in diabetics. Limited epitope mapping with the milk protein BSA identified one specific epitope, BSA(193), which was targeted by most MS but not diabetes patients. BSA(193) was encephalitogenic in SJL/J mice subjected to a standard protocol for the induction of experimental autoimmune encephalitis. These data extend the possible, immunological basis for the association of MS risk, CMP, and CNS autoimmunity. To pinpoint the same peptide, BSA(193), in encephalitis-prone humans and rodents may imply a common endogenous ligand, targeted through antigenic mimicry.
The Hospital For Sick Children, Research Institute, Toronto, Ontario, Canada.
S
S
Winer
I
I
Astsaturov
R K
RK
Cheung
K
K
Schrade
L
L
Gunaratnam
D D
DD
Wood
M A
MA
Moscarello
P
P
O'Connor
C
C
McKerlie
D J
DJ
Becker
H M
HM
Dosch
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000071797:Butyrophilins; D002364:Caseins / Q000276:immunology; D002417:Cattle; D003429:Cross Reactions; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D007782:Lactoglobulins / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000633:toxicity; D051379:Mice; D008815:Mice, Inbred Strains; D008894:Milk Proteins / Q000276:immunology* / Q000633:toxicity; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D010449:Peptide Mapping; D012710:Serum Albumin, Bovine / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D010566:Virulence Factors, Bordetella / Q000008:administration & dosage / Q000276:immunology
D000071797:Butyrophilins; D002364:Caseins; D018984:Epitopes, T-Lymphocyte; D007782:Lactoglobulins; D008562:Membrane Glycoproteins; D008894:Milk Proteins; D010446:Peptide Fragments; D010566:Virulence Factors, Bordetella; D012710:Serum Albumin, Bovine