Kono, Dwight H. and Urban, James L. and Horvath, Suzanna J. and Ando, Dale G. and Saavedra, Raul A. and Hood, Leroy (1988) Two minor determinants of myelin basic protein induce experimental allergic encephalomyelitis in SJL/J mice. Journal of Experimental Medicine, 168 (1). pp. 213-227. ISSN 0022-1007 http://resolver.caltech.edu/CaltechAUTHORS:20120621-075208217
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Experimental allergic encephalomyelitis (EAE)' is an autoimmune inflammatory demyelinating disease in the central nervous system (CNS) of animals immunized with myelin basic protein (MBP). The disease is directly mediated by Thelper cells that recognize MBP in the context ofclass II antigens of the MHC (1-3). In nude mice, a single clone of adoptively transferred MBP-reactive T helper cells can cause EAE (4), suggesting that these are the only T cells required for disease induction. As a prototypic model of T helper cell-mediated autoimmune disease, observations in EAE could likely be applicable to other T helper cell-mediated diseases such as murine lupus (5), thyroiditis (6), collagen arthritis (7), and adjuvant arthritis (8), as well as human autoimmune diseases. The MBP epitope is determined in part by the MHC. Using proteolytic peptide fragments of MBP, SJL/J (H-2s) and BIO.T(6R) (H-2q) mice were found to develop EAE to the COOH-terminal peptide of MBP, whereas PL/J (H-2u) and A/J (H-2k) mice developed EAE to the NH2-terminal peptide of MBP (9). Recently, by using synthetic peptides that overcome the difficulties of obtaining pure uncontaminated proteolytic peptides, a single T cell encephalitogenic epitope for PL/J mice has been identified . This epitope consists of the first nine NH2-terminal amino acid residues of MBP which must be acetylated at the a amino group to induce disease (10). Similar fine mapping of the encephalitogenic T cell epitope(s) for SJL/J mice has not been done, in part because of the large size of the COOH-terminal peptic fragment of MBP (residues 89-169 of rat MBP, reference 9). MouseMBP consists offour major forms due to differential RNA splicing of exons II and VI (11), resulting in molecular masses of 21, 18.5, 17.5, and 14 kD, in the relative amounts of 1 :10:3.5:35 . Since EAE can also be induced with the small form of rat MBP (14 kD), which has exons II and VI of the MBP gene deleted (12), the COOH-terminal encephalitogenic determinant for SJL/J mice must be present within a segment ofonly 42 amino acid residues . Consistent withthis notion is the observation that this peptide sequence is identical among the MBPs of several mammalian species, including mouse, rat, bovine, guinea pig, and porcine, all of which can induce EAE in SJL/mice (13, 14). To identify the SJL/J encephalitogenic T cell epitope(s), overlapping peptides to the COOH-terminal region ofthe small form of mouse MBP were synthesized. Two overlapping peptides encompassing an 18-amino acid region were found to elicit EAE in SJL/J mice. The finding of a single peptide region of MBP that is responsible for encephalitogenic T cell epitopes in SJL/J mice is analogous to that of the PL/J mice and has implications for the development of specific therapy for T cell-mediated autoimmune diseases.
|Additional Information:||© 1988 Rockefeller University Press. Received for publication 10 March 1988. D. H. Kono is a recipient of the Arthritis Investigator Award. J . L . Urban is a fellow of the Leukemia Society of America. R. A. Saavedra is a postdoctoral fellow of the National Multiple Sclerosis Society. We are grateful to Christine A. Acklin and Jill W. Jenik for their excellent work in peptide synthesis and purification, Eef Goedemans and Anita Ackerman for meticulous animal care, Bertha Jones for assistance with illustrations, and Cathy Elkins for preparation of the manuscript.|
|Official Citation:||Two minor determinants of myelin basic protein induce experimental allergic encephalomyelitis in SJL/J mice. D H Kono, J L Urban, S J Horvath, D G Ando, R A Saavedra, and L Hood 168:213-227. doi:10.1084/jem.168.1.213|
|Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Ruth Sustaita|
|Deposited On:||21 Jun 2012 16:02|
|Last Modified:||26 Dec 2012 15:21|
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