nitrophenols and Metabolic-Diseases

The ability to selectively induce a strong immune response against self-proteins, or increase the immunogenicity of specific epitopes in foreign antigens, would have a significant impact on the production of vaccines for cancer, protein-misfolding diseases, and infectious diseases. Here, we show that site-specific incorporation of an immunogenic unnatural amino acid into a protein of interest produces high-titer antibodies that cross-react with WT protein. Specifically, mutation of a single tyrosine residue (Tyr(86)) of murine tumor necrosis factor-alpha (mTNF-alpha) to p-nitrophenylalanine (pNO(2)Phe) induced a high-titer antibody response in mice, whereas no significant antibody response was observed for a Tyr(86) --> Phe mutant. The antibodies generated against the pNO(2)Phe are highly cross-reactive with native mTNF-alpha and protect mice against lipopolysaccharide (LPS)-induced death. This approach may provide a general method for inducing an antibody response to specific epitopes of self- and foreign antigens that lead to a neutralizing immune response.

Topics: Amino Acid Substitution; Animals; Antibody Formation; Communicable Diseases; Endotoxemia; Epitopes; Immunochemistry; Lipopolysaccharides; Male; Metabolic Diseases; Mice; Mutation, Missense; Neoplasms; Nitrophenols; Self Tolerance; Tumor Necrosis Factor-alpha; Vaccines

Topics: Adult; Amino Acids; Atropine; Cholinesterases; Female; Florida; Humans; Infant; Insecticides; Kidney Tubules; Male; Metabolic Diseases; Mortality; Nitrophenols; Parathion; Phosphates