Encephalitogenic activity of truncated myelin oligodendrocyte glycoprotein (MOG) peptides and their recognition by CD8+ MOG-specific T cells on oligomeric MHC class I molecules.
We have previously demonstrated that the 21-residue peptide pMOG(35-55) from myelin oligodendrocyte glycoprotein (MOG) contains an antigenic epitope that activates CD8(+) encephalitogenic T cells in C57BL/6 (B6) mice. To identify the core encephalitogenic epitope of CD8(+) MOG-specific T cells, we have prepared a panel of highly purified peptides of varying lengths, which span the entire length of pMOG(35-55), and tested their binding to recombinant H-2D(b) dimers and their ability to induce EAE. Two of the truncated peptides, pMOG(40-54) and pMOG(44-54), strongly bound recombinant H-2D(b) protein and this complex bound MOG-specific CD8(+) T cells. Interestingly, pMOG(40-54) retained the full capability of inducing paralytic disease, whereas only a part of the B6 mice immunized with pMOG(44-54) developed clinical paralysis and central nervous system (CNS) inflammation. Further deletion of 1 amino acid from either the N- or C-terminus of the peptide pMOG(44-54) dramatically reduced binding to recombinant H-2D(b), and abolished the induction of paralysis and CNS inflammation. Our results demonstrate that the ability of truncated pMOG(35-55) peptides to bind recombinant H-2D(b) protein does not always correlate with their ability of inducing encephalomyelitis. This approach enables the further identification of the core pathogenic epitope within the pMOG(35-55) that activates MOG-specific encephalitogenic CD8(+) T cells.
Sun
Deming
D
Kentucky Lions Eye Center, Department of Ophthalmology, and Vision Sciences, University of Louisville, Louisville, KY 40202, USA. d0sun001@louisville.edu
Zhang
Yiping
Y
Wei
Bingyuan
B
Peiper
Stephen C
SC
Shao
Hui
H
Kaplan
Henry J
HJ
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D004660:Encephalitis / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006825:Hybridomas / Q000378:metabolism; D051379:Mice; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism*; D063308:Myelin-Oligodendrocyte Glycoprotein; D010455:Peptides / Q000378:metabolism*
D015395:Histocompatibility Antigens Class I; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010455:Peptides