Sites in Myelin Basic Protein that React with Monoclonal Antibodies

Abstract

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.

Rat and Mouse Monoclonal Antibodies to Human Myelin Basic Protein

“…Addendum: While this manuscript was in preparation, a further report appeared on seven monoclonal antibodies evoked by guinea pig or monkey MBP rather than cleaved human MBP (Hruby et al, 1985). The properties of these antibodies differ in some respects from the properties of the antibodies described in the present work, especially in terms of species specificity (Hruby et al, 1985).…”

Evolutionary Divergence in the Structure of Myelin Basic Protein: Comparison of Chondrichthye Basic Proteins with Those from Higher Vertebrates

“…Guinea pigs and Lewis rats immunized with shark MBP , and guinea pigs immunized with dogfish MBP (Agrawal et al, 1971), have previously been reported to show no evidence of EAE. Since MBP has several antigenic determinants (Hruby et al, 1985) it is possible that the observed cellular immunity is directed toward a part of the antigen that is not involved in the induction of EAE in guinea pigs (Bergstrand, 1972;Spitler et al, 1972;Bergstrand and Kallen, 1973).…”

NMR and molecular dynamics studies of an autoimmune myelin basic protein peptide and its antagonist

“…It has been suggested [22,25] that the reduction in charge density on citrullinization of arginines (as occurs in multiple sclerosis) diminishes the interaction with negatively charged lipids in the myelin membrane, accounting for a certain amount of destabilization. The role of this strong positive net charge is also important in the MBP epitope studied (Gln74, Lys75, Gln77, Arg78, Gln80, Asn85) in comparison with the more positively charged Ala81 variant.…”

“…It was shown that MBP is a C-shaped molecule when adsorbed into a lipid monolayer, comprising five b-sheets and a large proportion of irregular coil. The lack of a high-resolution structure of MBP means that it is important to investigate the structure of its epitopes, found in segments 1-14, 22-34, 43-68, 67-75, 75-82, 83-96, 90-99, 114-121, 118-131, 125-131, 130-137 and 131-140 [23][24][25][26], which have antigenic properties. Characterization of the molecular features of these antigenic sites may provide insights into their immunogenic properties.…”