Myelin oligodendrocyte glycoprotein-35-55 peptide induces severe chronic experimental autoimmune encephalomyelitis in HLA-DR2-transgenic mice.
The use of HLA class II-transgenic (Tg) mice has facilitated identification of antigenic T cell epitopes that may contribute to inflammation in T cell-mediated diseases such as rheumatoid arthritis and multiple sclerosis (MS). In this study, we compared the encephalitogenic activity of three DR2-restricted myelin determinants [mouse (m) myelin oligodendrocyte glycoprotein (MOG)-35-55, human (h)MOG-35-55 and myelin basic protein (MBP)-87-99] in Tg mice expressing the MS-associated DR2 allele, DRB1*1501. We found that mMOG-35-55 peptide was strongly immunogenic and induced moderately severe chronic experimental autoimmune encephalomyelitis (EAE) with white matter lesions after a single injection in Freund's complete adjuvant followed by pertussis toxin. hMOG-35-55 peptide,which differs from mMOG-35-55 peptide by a proline for serine substitution at position 42, was also immunogenic, but not encephalitogenic, and was only partially cross-reactive with mMOG-35-55. In contrast, MBP-87-99, which can induce EAE in double-Tg mice expressing both HLA-DR2 and a human MBP-specific TCR, was completely non-encephalitogenic in HLA-DR2-Tg mice lacking the human TCR transgene. These findings demonstrate potent encephalitogenic activity of the mMOG-35-55 peptide in association with HLA-DR2, thus providing a strong rationale for further study of hMOG-35-55 peptide as a potential pathogenic determinant in humans.
Rich
Cathleen
C
Veterans Affairs Medical Center, Portland, OR 97207, USA.
Link
Jason M
JM
Zamora
Alex
A
Jacobsen
Helle
H
Meza-Romero
Roberto
R
Offner
Halina
H
Jones
Richard
R
Burrows
Gregory G
GG
Fugger
Lars
L
Vandenbark
Arthur A
AA
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001665:Binding Sites; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000378:metabolism*; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism*; D015802:HLA-DR2 Antigen / Q000235:genetics* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology
D000906:Antibodies; D006023:Glycoproteins; D015802:HLA-DR2 Antigen; D000949:Histocompatibility Antigens Class II; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55)