UNMASKING OF AN UNUSUAL MYELIN BASIC-PROTEIN EPITOPE DURING THE PROCESS OF MYELIN DEGENERATION IN HUMANS - A POTENTIAL MECHANISM FOR THE GENERATION OF AUTOANTIGENS

A rabbit antiserum (anti-EP), induced against a synthetic peptide corr esponding to residues 68 to 86 of guinea pig myelin basic protein, pow erfully immunostained abnormal-appearing oligodendrocytic processes an d cell bodies in demyelinating areas associated with multiple sclerosi s plaques. However, it failed to recognize any structures in normal hu man, rat, or guinea pig brain. The antiserum recognized the synthetic peptide QDENPVV, which corresponds to human myelin basic protein resid ues 82 to 88. Immuno-absorption with this peptide eliminated immunohis tochemical staining. By contrast, several commercial antibodies recogn izing nearby sequences of human myelin basic protein intensely stained all myelinated structures ill both normal and multiple sclerosis tiss ue. The unusual epitope recognized by anti-EP appears to be accessible only in areas of myelin degeneration. If insults occur that repeatedl y expose a region of MBP normally sheltered from immunosurveillance, a self-sustaining immune reaction might result.