Autoimmune epitopes: autoepitopes.
The identity of reactants for autoantibodies has been successively refined from whole cellular organelles (immunofluorescence), identified molecules (immunoblot; gene expression libraries), epitope regions (truncated cDNAs; peptide scanning) to contact residues, as described here. Most autoantibodies react with conformational epitopes, in which amino acids distant in the linear sequence come into contiguity by protein folding. Identification of contact sites with the antibody paratope requires particular technologies, crystallography, or antibody screening of phage-displayed random peptide libraries. The latter is illustrated by our studies on the autoepitope for anti-PDC-E2 (AMA) in primary biliary cirrhosis (PBC), anti-GAD65 in type 1 diabetes, and anti-C1 of type II collagen in collagen-induced arthritis. More precise definition of the structure of conformational autoepitopes could (a) clarify controversial aspects of autoimmunity including epitope mimicry, epitope spreading, and molecular spatial relationships between B and T cell autoepitopes, and (b) impact on novel diagnostic and therapeutic (vaccine) molecules.
Mackay
Ian R
IR
Department of Biochemistry and Molecular Biology, Monash University Clayton, 3800, Victoria, Australia. ian.mackay@med.monash.edu.au
Rowley
Merrill J
MJ
D000818:Animals; D001168:Arthritis / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D024043:Collagen Type II / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology; D051047:Dihydrolipoyllysine-Residue Acetyltransferase; D000939:Epitopes / Q000276:immunology*; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000276:immunology; D011768:Pyruvate Dehydrogenase Complex / Q000276:immunology
D024043:Collagen Type II; D000939:Epitopes; D011768:Pyruvate Dehydrogenase Complex; D051047:Dihydrolipoyllysine-Residue Acetyltransferase; D005968:Glutamate Decarboxylase