IMMUNOREACTIVITY OF PMP-22, P0, AND OTHER 19 TO 28 KDA GLYCOPROTEINS IN PERIPHERAL-NERVE MYELIN OF MAMMALS AND FISH WITH HNK1 AND RELATED ANTIBODIES

Mammalian peripheral nervous system (PNS) myelin contains several glyc oproteins with molecular weights of 19 to 28 kDa, including the major 28 kDa P0 glycoprotein and a recently cloned protein called PMP-22. So me glycoproteins in this M(r) range in humans, cats and some other mam mals react with HNK1, a mouse monoclonal antibody that identifies a ca rbohydrate epitope shared between the immune system and a number of ad hesion proteins in the nervous system. A variety of antibodies to P0, PMP-22, and the carbohydrate determinants reacting with HNK1 were used to characterize immunochemically these 19 to 28 kDa glycoproteins of cat PNS myelin. The HNK1-reactive components include P0 and two slight ly smaller 23 to 26 kDa proteins that are immunologically related to P 0. However, HNK1 reacts most strongly with a lower molecular weight gl ycoprotein that does not react with the antibodies to P0 and was ident ified as PMP-22. Since the carbohydrate structure reacting with HNK1 i s generally expressed on adhesion molecules, this result suggests that PMP-22 may function in cell-cell or membrane-membrane interactions. F urthermore, the related human anti-MAG monoclonal IgM antibodies from patients with neuropathy also react strongly with PMP-22, suggesting t hat it may be a target antigen in the pathogenesis of this disease. Pu rified PNS and CNS myelin from bony fish (toadfish and trout) were als o shown to contain major glycoproteins, in the same 19 to 28 kDa M(r) range, that react very strongly with HNK1. It is known that fish myeli n has major proteins of this size that are immunologically and structu rally related to mammalian P0, and it is demonstrated here that one of the strongly HNK1-positive proteins reacted well with an antiserum ra ised to bovine P0. The presence of high levels of the adhesion-related HNK1 epitope on these major myelin proteins of fish suggests that thi s carbohydrate structure may have played a role in the molecular evolu tion of myelin. (C) 1993 Wiley-Liss, Inc.