Allergic neuritis: phospholipid requirement for the disease-inducing conformation of the P2 protein.
The P2 protein, a small, highly ordered basic protein of peripheral nerve myelin, is a potent inducer of allergic neuritis in rats when complexed with phospholipids such as phosphatidylserine. Isolated P2 protein administered without lipid is a poor neuritogen, and if first oxidized with performic acid, aminoethylated in 8 M urea or heat denatured, it loses nearly all activity. When the aminoethylated or oxidized forms are combined with phosphatidylserine, however, they recover essentially full neuritogenic activity. Complexing with lipid also greatly enhances the activity of the heart denatured form. Spleen cells sensitized to the aminoethylated and heated forms of P2 protein show a pronounced mitogenic response to either of these forms as well as to the P2 protein itself, but only when sensitization is initiated with the lipid complex. These data indicate that the lipid complex reverses the distortion acquired by chemical treatment or denaturation and converts the P2 molecule into a conformation approximating that of the native P2 protein in myelin. These studies imply that the neuritogenic domain, while highly sensitive to denaturing conditions, requires interaction with phospholipids in order to attain the most favourable conformation for inducing a cell-mediated response that leads to disease.
D000818:Animals; D000941:Antigens; D001327:Autoimmune Diseases / Q000209:etiology*; D007120:Immunochemistry; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D004676:Myelin Basic Protein / Q000276:immunology*; D018996:Myelin P2 Protein; D009443:Neuritis / Q000209:etiology*; D010718:Phosphatidylserines / Q000276:immunology; D010743:Phospholipids / Q000276:immunology*; D011487:Protein Conformation; D011817:Rabbits; D051381:Rats
D000941:Antigens; D004676:Myelin Basic Protein; D018996:Myelin P2 Protein; D010718:Phosphatidylserines; D010743:Phospholipids