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.
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.
Linington
C
C
Department of Neuroimmunology, Max-Planck-Institute for Psychiatry, Planegg-Martinsried, FRG.
Lassmann
H
H
Ozawa
K
K
Kosin
S
S
Mongan
L
L
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002460:Cell Line; D005803:Genes, Immunoglobulin; D016219:Immunotherapy, Adoptive; D008969:Molecular Sequence Data; D018993:Myelin P0 Protein; D009185:Myelin Proteins / Q000276:immunology*; D009444:Neuritis, Autoimmune, Experimental / Q000209:etiology*; D010446:Peptide Fragments / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology*
D001324:Autoantigens; D015815:Cell Adhesion Molecules; D018993:Myelin P0 Protein; D009185:Myelin Proteins; D010446:Peptide Fragments