Biological Activity and Synthesis of an Encephalitogenic Determinant

Shapira, Raymond; Chou, Fch; McKneally, S S; Urban, Ernst; Kibler, Robert F.

doi:10.1126/science.173.3998.736

Cited by 98 publications

(31 citation statements)

References 8 publications

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“…On the other hand, rabbits respond much more vigorously to these regions. Fragment 44-89 is a major encephalitogenic region when tested in rabbits [6,7,11,131 we extend previous studies concerning the encephalitogenic activity of the C-terminal region of the bovine protein when tested in rabbits. We present evidence that there are at least two different disease-inducing sites in this part of the protein localized within the sequences 134-150 and 154-170, respectively.…”

Section: Introductionsupporting

confidence: 74%

Encephalitogenic activity in rabbits of the C‐terminal region of bovine basic myelin protein: Localization to two different regions

Bergstrand

1972

FEBS Letters

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Section: Introductionsupporting

confidence: 74%

Encephalitogenic activity in rabbits of the C‐terminal region of bovine basic myelin protein: Localization to two different regions

Bergstrand

1972

FEBS Letters

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“…Third, the observed "cross reactivity" between region 1 -116 and 117-170 might depend on a similar "immunochemical" configuration of two sequences, one situated in region 1-90 and onc in 117-170, and thus does not, as hitherto supposed, reflect the presence of a common determinant in region 90-116. Shapira et al reported recently [7,38] the synthesis of a decapeptide which is encephalitogenic in rabbits. The stereochemical configuration of this peptide is said to show striking similarities to the previously synthesized tryptophan-containing region.…”

Section: Antigenic Determinants On Bovine Encephalitogenic Proteinmentioning

confidence: 99%

Localization of Antigenic Determinants on Bovine Encephalitogenic Protein

Bergstrand

1972

European Journal of Biochemistry

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By peptic or tryptic proteolysis of different fragments of bovine encephalitogenic protein, a set of small fragments covering the following regions of the native protein have been obtained: 44-68, 44-89, 75-91, 93-116, 114-130, 134-150, and 154-170 (the amino acid residues are numbered according to [l]). These fragments were used in the macrophage migration inhibition technique in guinea pigs (an assay which is vividly considered as a correlate in vitro to delayed type hypersensitivity) to study the localization of antigenic determinants in the protein.The results indicate the presence of a t least one determinant in each of regions 44-68, 134-140, and 154-170. Furthermore, the rather strong determinant, which has previously been localized around the single tryptophan residue in the protein does not seem to be contained within peptide 114-130, as this peptide is considered unreactive in the assay. On the other hand, this peptide shows full encephalitogenic activity.Experimental allergic encephalomyelitis is an experimentally induced disease in animals, which is considered to be predominantly due to a cell-mediated autoimmunity against central nervous system myelin [2]. The disease-inducing component of the myelin is a strongly basic protein which has been well characterized [l -61. This encephalitogenic protein (from bovine tissue) has been shown to have a t least four different sites capable of inducing the disease in rabbits [7-91. The activities of these sites seem to vary considerably. Guinea pigs, on the other hand, respond predominantly to only one of these regions, whereas the others have marginal, if any, activity [9-111. Investigations in this laboratory have been concerned with the relation between disease-inducing sites and antigenic determinants on the protein. I n a recent report [12] we described the isolation and partial characterization of a set of different proteolytically and chemically derived fragments of bovine encephalitogenic protein. These fragments have been used to study antigenic determinants on the protein capable of reacting in the macrophage migration inhibition test, which is a well-documented correlate in vitro to delayed type hypersensitivity.There could be demonstrated 1131 a t least four different reactive regions in the protein with the apparently most reactive sequence containing the single tryptophan residue in position 116.I n the present communication, attempts a t a narrower localization of the determinants are described, using a new set of fragments and the macrophage migration inhibition assay in guinea pigs. MATERIALS AND METHODSPepsin (P-6875 Lot 7OC-0280) and trypsin (T-1005 Lot 7OC-8070) were both obtained from Sigma Chemical Company. Fig.1 shows the schematical description of the preparation of the different fragments. Preparation of the Different PolypeptidesThe isolation and characterization of fragments 44-116, 90-170, and 117-170, which provided starting material for the preparation of new fragments, has previously been described in detail [12].Fragments 44-89 ...

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“…The encephalitogenic contribution of each of the amino acids from the tryptophan region, fswgaegqr, has been examined thoroughly in the guinea pig (8,29,37,43,44,47,50). The midpeptide, tthygslpqk, has been studied in the DR rat and rabbit (31,33). The hyperacute EAE site, pqksqrtqdenpv, has been analyzed in the Lewis rat (20-22, 45, 52).…”

Section: Methodsmentioning

confidence: 99%

Molecular Mimicry Revisited: Gut Bacteria and Multiple Sclerosis

Westall¹

2006

J Clin Microbiol

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Molecular mimicry is a possible explanation for autoimmune side effects of microorganism infections. Protein sequences from a particular microorganism are compared to known autoimmune immunogens. For diseases such as multiple sclerosis (MS), where the infectious agent is unknown, guesses to its identity are made. Mimics are assumed to be rare. This study takes a radically different approach. Reported sequences from all known human bacterial and viral agents were searched for autoimmune immunogen mimics. Three encephalitogenic peptides, whose autoimmune requirements have been studied extensively, were selected for comparison. Mimics were seen in a wide variety of organisms. For each immunogen, the mimics were found predominantly in nonpathogenic gut bacteria. Since the three immunogens used in this study are related to MS, it is suggested that a microorganism responsible for autoimmune activity in MS could be a normally occurring gut bacterium. This would explain many of the peculiar MS epidemiological data and why no infective agent has been identified for MS and supports recently found MS gut metabolism abnormalities.

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Biological Activity and Synthesis of an Encephalitogenic Determinant

Cited by 98 publications

References 8 publications

Encephalitogenic activity in rabbits of the C‐terminal region of bovine basic myelin protein: Localization to two different regions

Encephalitogenic activity in rabbits of the C‐terminal region of bovine basic myelin protein: Localization to two different regions

Localization of Antigenic Determinants on Bovine Encephalitogenic Protein

Molecular Mimicry Revisited: Gut Bacteria and Multiple Sclerosis

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