Cell adhesion molecules of the immunoglobulin supergene family as tissue-specific autoantigens: induction of experimental allergic neuritis (EAN) by P0 protein-specific T cell lines

Eur J Immunol. 1992 Jul;22(7):1813-7. doi: 10.1002/eji.1830220721.


The P0 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 P0 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 P0, while the other disease-inducing T cell epitope (residues 180-199) is located within the proteins cytoplasmic carboxyterminal domain. The adoptive transfer of 10(6) 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 P0 protein or the native membrane-bound P0 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Autoantigens / immunology*
  • Cell Adhesion Molecules / immunology*
  • Cell Line
  • Genes, Immunoglobulin*
  • Immunotherapy, Adoptive
  • Molecular Sequence Data
  • Myelin P0 Protein
  • Myelin Proteins / immunology*
  • Neuritis, Autoimmune, Experimental / etiology*
  • Peptide Fragments / immunology
  • Rats
  • Rats, Inbred Lew
  • T-Lymphocytes / immunology*


  • Autoantigens
  • Cell Adhesion Molecules
  • Myelin P0 Protein
  • Myelin Proteins
  • Peptide Fragments