Experimental Allergic Encephalitis

Abstract

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.

Linkage of Susceptibility to Experimental Allergic Encephalomyelitis to the Major Histocompatibility Locus in the Rat

“…Thus, even when immunized with such a complex antigenic mixture as whole spinal cord, the susceptibility to EAE induction behaves according to predictions based on a single Ir-gene linked to the major histocompatibility locus. The possible existence of Ir-EAE genes in other species would also offer some explanation for nonuniform reactivity among outbred animals tested with various basic protein fraganents (14). The extent to which EAE is a model for human demyelinating diseases such as multiple sclerosis would be strengthened if the correlation of susceptibility and certain HL-A specificities reflects Ir gene participation in the human disease.…”

Molecular Mimicry Revisited: Gut Bacteria and Multiple Sclerosis

“…Here again, these children were not suffering from EAE, MS, or cancer. Finally, Spitler et al (34,35) showed that guinea pigs sensitized with encephalitogenic peptides having amino acid sequences different from that in the test protein did not show cellular immunity in vivo or in vitro to myelin basic protein, although the animals developed EAE. Einstein (6a) showed that antigen (MBP) suppression of EAE in guinea pigs did not require an intact tryptophan, and yet the tryptophan is an absolute requirement for disease induction.…”

A Common Tumour Specific Antigen

“…However, the delayed cutaneous hypersensitivity reaction and the release of macrophage slowing factor (as opposed to migration inhibition factor, MIF) are not necessarily linked aspects of the total immune response, as has been noted in studies of other aspects of cellular immunity (Swanborg, 1969;Macfarland and Heilman, 1966;Bergstrand, 1972;Spitler et al, 1972;Bach et al, 1972;Hughes and Paty, 1971).…”