A rheumatoid factor specific mimotope identified by a peptide display library.
We screened a 10 amino acid peptide display library in filamentous phage with B'20, a monoclonal high affinity IgM rheumatoid factor (RF) expressing the VkIIIa-dependent 4C9 idiotype. Using direct and indirect selection techniques, 12 B'20 reactive peptides were identified, 9 of which belonged to one of two motifs. Binding of B'20 to phage-bearing peptides was inhibited by both IgG and 4C9 antiidiotype. Synthetic peptides corresponding to the two motifs inhibited the Fc binding of a low avidity IgA B'20 construct. Purified IgM from 6/8 RF-positive RA patients and 8/11 monoclonal RFs with VkIII-encoded light chains bound to the phage, whereas none of the four monoclonal RFs with VkI or VkII encoded light chains bound. Phage binding appeared to be RF specific. Three 4C9 positive/RF negative cell lines from RA patients did not bind to phage nor did three B'20 mutants that had lost RF specificity, whereas two mutants that retained RF specificity also retained phage binding. We propose that there is a common epitope(s) recognized by VkIII encoded RFs that is mimicked by the structure of these peptides. Such mimotopes might be exploited to design novel agents that interfere with autoantibody binding.
Zhang
M
M
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Davidson
A
A
D000911:Antibodies, Monoclonal / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001435:Bacteriophages / Q000235:genetics / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D005803:Genes, Immunoglobulin; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology*; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology; D012217:Rheumatoid Factor / Q000235:genetics / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D007075:Immunoglobulin M; D019151:Peptide Library; D010455:Peptides; D012217:Rheumatoid Factor