A monoclonal antibody (immunoglobulin G1) has been produced that reacts against myelin basic protein present in or extracted from the brains of many mammals-with certain important exceptions. Because of known species differences in amino acid sequences of basic protein and of certain peptide fragments, the binding site for this particular antibody appeared likely to include residues 130 to 137. Confirmation of this hypothesis was obtained by amino acid composition of the major immunoreactive peptides produced by thermolysin digestion of human basic protein and isolated by high-performance liquid chromatography.
The epitopes (antigenic sites) for seven monoclonal antibodies (MAbs) evoked in rats or mice by guinea pig or monkey myelin basic protein (BP) have been located in four different sequences of the BPs extracted from various species. Six of the MAbs were evoked by guinea pig BP. (1) One epitope, possibly a pair, is included within residues 1-14 of all BPs tested and reacts with two rat IgG MAbs. (2) A definite pair of overlapping epitopes includes the central Phe91-Phe92 sequence. One epitope is contained entirely within sequence 90-99 and reacts with a rat IgG MAb. The substitution of Ser in chicken BP for Thr97 destroys this epitope. The other epitope appears to include residues on the amino side of Phe44 and even of His32 and suggests some tertiary structure in BP. This epitope reacts with a mouse IgM MAb that does not recognize the chicken substitution. (3) The third epitope lies within residues 114-121, specifically including Trp118, and reacts with a rat IgG MAb. A cross-reacting epitope probably includes residues 44-45 in certain species (guinea pig and bovine but not rabbit). (4) Another pair of epitopes is located within residues 131-140 but is severely species-restricted. This region in guinea pig BP evoked a species-specific mouse IgM MAb. The same region in monkey BP evoked the seventh MAb, a mouse IgG, which reacts with human, chimpanzee, monkey, bovine, and rat-18.5 kDa BPs and to a lesser extent rabbit BP but not with guinea pig, pig, or chicken BPs. Some tertiary structure in guinea pig BP is also suggested by the reactivities with the IgM MAb. All of the MAbs react with myelin in histologic preparations, but the optimum method of preparation of the tissue varies with each.
The potential use of quantitative MRI to characterize early, as well as late, immune-mediated lesions of multiple sclerosis (MS) has been investigated. Experimental allergic encephalomyelitis (EAE) was induced in 4 male Macaca fascicularis monkeys, and the development of the disease followed using quantitative MRI at 0.15 Tesla. Serial scans were recorded daily, beginning at day 9 after inoculation. Lesions were detected before the onset of clinical signs, due to an elevation in the spin-lattice (T1) and spin-spin (T2) relaxation times. The T1 and T2 values from the lesions were shown to increase over time, indicative of progressive change at a molecular level. The appearance of any new lesions and any changes in existing ones were noted; this allowed dating of the lesions postmortem. Pathological correlation showed the long T1 and T2 values to be associated with the presence of inflammation, demyelination and haemorrhagic necrosis. Microscopically similar lesions had the same MRI characteristics. In addition, these studies showed the oldest lesions to be the most haemorrhagic; this is contrary to the belief that haemorrhage is a secondary event in EAE. The results show that quantitative MRI is sensitive to variable pathology, and has the potential for use in characterizing the pathological progression in MS.
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