Cell adhesion molecules of the immunoglobulin supergene family as tissue‐specific autoantigens: induction of experimental allergic neuritis (EAN) by PO protein‐specific T cell lines

Abstract

The PO glycoprotein is a homophilic cell adhesion molecule of the immunoglobulin supergene family which is responsible for maintaining the structure of compact internodal myelin in the peripheral nervous system (PNS). Utilizing a panel of synthetic PO peptides two distinct T cell epitopes have been identified that can induce T cell-mediated experimental autoimmune neuritis (EAN) in the Lewis rat. One T cell epitope (amino acid residues 56–71), is located within the extracellular, immunoglobulin-like domain of PO, while the other disease-inducing T cell epitope (residues 180–199) is located within the proteins cytoplasmic carboxyterminal domain. The adoptive transfer of 10⁶ CD4⁺ T line cells specific for either of these peptide antigens induced EAN in syngeneic recipients. However, while the pathogenic response induced by both peptide-specific T cell lines was identical, their epitopes differ markedly in their immunologic properties in vivo. In particular while the response to peptide p180–199 was immunodominant in animals immunized with either purified PO protein or the native membrane-bound PO protein in autologous rat peripheral nerve myelin, no response to peptide p56–71 was detected, indicating that this epitope is cryptic. This study provides the first experimental evidence that the immunoglobulin-like domains of members of the immunoglobulin supergene family can function as target autoantigens in T cell-mediated autoimmune disease.