A new epitope on human myelin basic protein arising from cleavage by a metalloendoprotease associated with brain myelin membranes.

Human brain myelin membranes were incubated to allow activity of an associated metalloendoprotease which cleaves myelin basic protein (MBP). A 10.3 kDa C-terminal fragment of MBP, peptide C, isolated from the incubation medium had a blocked N-terminal. After treatment with pyroglutamyl aminopeptidase, N-terminal sequencing indicated that Gln74 of MBP formed the N-terminal residue of peptide C. A rabbit antiserum was raised to a synthetic peptide containing the sequence Pyroglu-Lys-Ser-His-Gly-Arg, corresponding to the first six residues of peptide C. By immunoblotting this serum reacted with peptide C but not with intact MBP. The data indicate that cleavage of MBP by a myelin-associated protease engenders a new epitope.