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More MS news articles for February 2003

Encephalitogenic activity of truncated myelin oligodendrocyte glycoprotein (MOG) peptides and their recognition by CD8(+) MOG-specific T cells on oligomeric MHC class I molecules

Int Immunol 2003 Feb;15(2):261-268
Sun D, Zhang Y, Wei B, Peiper SC, Shao H, Kaplan HJ.
Kentucky Lions Eye Center, Department of Ophthalmology, and Vision Sciences, and James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA Department of Neurology, University of California Irvine, Irvine, CA 92697-4275, USA BD Biosciences PharMingen, San Diego, CA 92121, USA.

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.