Myelin/oligodendrocyte glycoprotein is a unique member of the immunoglobulin superfamily

Abstract

Myelin/oligodendrocyte glycoprotein (MOG) is a primary target autoantigen in experimental autoimmune encephalomyelitis, a widely used animal model for autoimmune demyelinating diseases such as multiple sclerosis. We have isolated several rat MOG cDNAs and confirmed their identity by comparision with MOG N‐terminal peptide sequence. As expected, MOG mRNA expression is CNS‐specific and peaks during active myelination. Our studies show that full length MOG mRNA is ≈︁ 1.6 kb and encodes a signal peptide of 27 amino acids, followed by 218 residues for mature MOG (24,962 MW). A single site for N‐glycosylation is found at Asn‐31. Rather than the ubiquitous AAUAAA polyadenylation signal, a series of three overlapping, rare poly A signals were identified. The N‐terminal half of mature MOG shares 52% identity with bovine butyrophilin, a possible lipid receptor. This same region has 39% identity with chicken B‐G antigen, a major histocompatibility complex antigen involved in B cell selection and immune repertoire development. We show that both MOG and butyrophilin, each exhibiting a single Ig like variable region domain, meet criteria for inclusion in the immunoglobulin superfamily. Moreover, MOG appears to represent a unique member of this superfamily in that it possesses two potential transmembrane domains, in contrast to a single membrane‐spanning domain or glycophospholipid anchor found in all other members of Ig superfamily members. © 1992 Wiley‐Liss, Inc.