The encephalitogenic determinant of brain protein, a nonapeptide having the amino acid sequence Phe-Ser-Trp-Gly-Ala-Glu-Gly-Gln-Lys, has been characterized and synthesized. In a previous study, analogues of this encephalitogenic peptide were synthesized and some were shown to be encephalitogenic while others were not. Guinea pigs were immunized with encephalitogenic peptides having amino acid sequences different from that in the native protein. These guinea pigs did not show cellular immunity in vivo (skin reactivity) or in vitro (lymphocyte stimulation or macrophage migration inhibition) to the encephalitogenic brain protein (EP) although they did show cellular immunity to the immunizing antigenic peptide. Guinea pigs immunized with an encephalitogenic peptide having the same amino acid sequence as the brain protein, or with a nonencephalitogenic peptide having the same amino acid sequence as the native protein but lacking the terminal lysine, did develop cellular immunity to the EP. Animals immunized with EP showed cellular immunity to this protein, but not to the encephalitogenic peptides. Animals immunized with nonencephalitogenic protein (NEP), prepared by altering the tryptophan residue of EP, did not develop disease but did show cellular immunity in vitro and in vivo to the EP. Animals protected from disease by immunization with NEP similarly showed cellular immunity to EP. Thus, the results suggest a dissociation between cellular immunity to EP and the production of experimental allergic encephalitis (EAE). Animals immunized with the encephalitogenic peptides develop EAE, but do not show cellular immunity to EP, and animals immunized with NEP show cellular immunity to EP but do not develop EAE. A fresh approach to the examination of the pathogenesis of EAE is now possible through the use of these well-characterized antigens.
Article|
July 01 1972
EXPERIMENTAL ALLERGIC ENCEPHALITIS : DISSOCIATION OF CELLULAR IMMUNITY TO BRAIN PROTEIN AND DISEASE PRODUCTION
Lynn E. Spitler,
Lynn E. Spitler
From the Section of Hematology and Immunology, Department of Medicine, University of California San Francisco Medical Center, San Francisco, California 94122, and the Salk Institute, San Diego, California 92112
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Christine M. von Muller,
Christine M. von Muller
From the Section of Hematology and Immunology, Department of Medicine, University of California San Francisco Medical Center, San Francisco, California 94122, and the Salk Institute, San Diego, California 92112
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H. Hugh Fudenberg,
H. Hugh Fudenberg
From the Section of Hematology and Immunology, Department of Medicine, University of California San Francisco Medical Center, San Francisco, California 94122, and the Salk Institute, San Diego, California 92112
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Edwin H. Eylar
Edwin H. Eylar
From the Section of Hematology and Immunology, Department of Medicine, University of California San Francisco Medical Center, San Francisco, California 94122, and the Salk Institute, San Diego, California 92112
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Lynn E. Spitler
From the Section of Hematology and Immunology, Department of Medicine, University of California San Francisco Medical Center, San Francisco, California 94122, and the Salk Institute, San Diego, California 92112
Christine M. von Muller
From the Section of Hematology and Immunology, Department of Medicine, University of California San Francisco Medical Center, San Francisco, California 94122, and the Salk Institute, San Diego, California 92112
H. Hugh Fudenberg
From the Section of Hematology and Immunology, Department of Medicine, University of California San Francisco Medical Center, San Francisco, California 94122, and the Salk Institute, San Diego, California 92112
Edwin H. Eylar
From the Section of Hematology and Immunology, Department of Medicine, University of California San Francisco Medical Center, San Francisco, California 94122, and the Salk Institute, San Diego, California 92112
Received:
March 12 1972
Online ISSN: 1540-9538
Print ISSN: 0022-1007
Copyright © 1972 by The Rockefeller University Press
1972
J Exp Med (1972) 136 (1): 156–174.
Article history
Received:
March 12 1972
Citation
Lynn E. Spitler, Christine M. von Muller, H. Hugh Fudenberg, Edwin H. Eylar; EXPERIMENTAL ALLERGIC ENCEPHALITIS : DISSOCIATION OF CELLULAR IMMUNITY TO BRAIN PROTEIN AND DISEASE PRODUCTION . J Exp Med 1 July 1972; 136 (1): 156–174. doi: https://doi.org/10.1084/jem.136.1.156
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