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Inhibition by serum of encephalitogenic activity of myelin basic protein
Abstract:
Basic protein of myelin from bovine brain (B-BPM) in Freund's complete adjuvant (FCA) is highly encephalitogenic for the guinea pig. However, when B-BPM is mixed with serum from various species it loses its encephalitogenic effect but not its immunogenic properties. When the synthetic tryptophan peptide matching residue 115-126 of human BPM is mixed with normal human serum it loses both its encephalitogenic and immunogenic effects. The time of exposure to serum necessary for complete inhibition of encephalitogenic activity of B-BPM varied: rat, horse, sheep and human sera produced their inhibitory effect immediately after mixing, whereas guinea pig serum required 8h. The capacity of serum to abrogate the encephalitogenic effects of B-BPM was not due to complete degradation of the molecule by proteinases in serum, because all animals injected with the B-BPM serum mixture gave cutaneous delayed hypersensitivity reactions to B-BPM. The inhibitory effect could be attributed to a factor in serum which is non-dialysable, thermostable at 56 degrees C, for 1 h, and present in high concentration in fetal calf serum. It may be an alpha2 macroglobulin which can act selectively on the main encephalitogenic determinant, around or within residues 115-126 of the basic protein of myelin.
Insights
Serum factors can inhibit the encephalitogenic potential of bovine basic myelin protein (B-BPM), preventing experimental allergic encephalomyelitis. This inhibition preserves immunogenicity, suggesting a targeted mechanism rather than degradation.
Area of Science:
- Neuroimmunology
- Protein chemistry
Background:
- Basic protein of myelin (BPM) from bovine brain (B-BPM) is encephalitogenic in guinea pigs.
- Encephalitogenicity is the capacity to induce inflammation in the brain.
Purpose of the Study:
- To investigate the effect of serum on the encephalitogenic and immunogenic properties of B-BPM.
- To characterize the factor(s) in serum responsible for inhibiting encephalitogenicity.
Main Methods:
- Mixing B-BPM with sera from various species and assessing encephalitogenicity in guinea pigs.
- Testing immunogenicity via cutaneous delayed hypersensitivity reactions.
- Characterizing the inhibitory factor's properties (dialysis, heat stability, concentration).
Main Results:
- Serum exposure abolished B-BPM's encephalitogenic effect but not its immunogenicity.
- Inhibition varied by species, with guinea pig serum requiring longer exposure.
- The inhibitory factor is non-dialysable, heat-stable, and present in high concentrations in fetal calf serum.
- The factor likely targets the encephalitogenic determinant (residues 115-126) without degrading the protein.
Conclusions:
- Serum contains factors, potentially alpha2 macroglobulin, that inhibit BPM-induced encephalomyelitis.
- This inhibition is selective for the encephalitogenic determinant, preserving immune recognition.