epidermal-growth-factor and 3-nitrotyrosine

epidermal-growth-factor has been researched along with 3-nitrotyrosine* in 1 studies

Other Studies

1 other study(ies) available for epidermal-growth-factor and 3-nitrotyrosine

Article	Year
Loss of CD4 T-cell-dependent tolerance to proteins with modified amino acids. Proceedings of the National Academy of Sciences of the United States of America, 2011, Aug-02, Volume: 108, Issue:31 The site-specific incorporation of the unnatural amino acid p-nitrophenylalanine (pNO(2)Phe) into autologous proteins overcomes self-tolerance and induces a long-lasting polyclonal IgG antibody response. To determine the molecular mechanism by which such simple modifications to amino acids are able to induce autoantibodies, we incorporated pNO(2)Phe, sulfotyrosine (SO(3)Tyr), and 3-nitrotyrosine (3NO(2)Tyr) at specific sites in murine TNF-α and EGF. A subset of TNF-α and EGF mutants with these nitrated or sulfated residues is highly immunogenic and induces antibodies against the unaltered native protein. Analysis of the immune response to the TNF-α mutants in different strains of mice that are congenic for the H-2 locus indicates that CD4 T-cell recognition is necessary for autoantibody production. IFN-γ ELISPOT analysis of CD4 T cells isolated from vaccinated mice demonstrates that peptides with mutated residues, but not the wild-type residues, are recognized. Immunization of these peptides revealed that a CD4 repertoire exists for the mutated peptides but is lacking for the wild-type peptides and that the mutated residues are processed, loaded, and presented on the I-A(b) molecule. Overall, our results illustrate that, although autoantibodies are generated against the endogenous protein, CD4 cells are activated through a neo-epitope recognition mechanism. Therefore, tolerance is maintained at a CD4 level but is broken at the level of antibody production. Finally, these results suggest that naturally occurring posttranslational modifications such as nitration may play a role in antibody-mediated autoimmune disorders. Topics: Amino Acid Substitution; Amino Acids; Animals; Autoantibodies; CD4-Positive T-Lymphocytes; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Epitopes; Female; Immune Tolerance; Immunization; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Mutant Proteins; Phenylalanine; Time Factors; Tumor Necrosis Factor-alpha; Tyrosine	2011

Article

Year

Loss of CD4 T-cell-dependent tolerance to proteins with modified amino acids.

Proceedings of the National Academy of Sciences of the United States of America, 2011, Aug-02, Volume: 108, Issue:31

The site-specific incorporation of the unnatural amino acid p-nitrophenylalanine (pNO(2)Phe) into autologous proteins overcomes self-tolerance and induces a long-lasting polyclonal IgG antibody response. To determine the molecular mechanism by which such simple modifications to amino acids are able to induce autoantibodies, we incorporated pNO(2)Phe, sulfotyrosine (SO(3)Tyr), and 3-nitrotyrosine (3NO(2)Tyr) at specific sites in murine TNF-α and EGF. A subset of TNF-α and EGF mutants with these nitrated or sulfated residues is highly immunogenic and induces antibodies against the unaltered native protein. Analysis of the immune response to the TNF-α mutants in different strains of mice that are congenic for the H-2 locus indicates that CD4 T-cell recognition is necessary for autoantibody production. IFN-γ ELISPOT analysis of CD4 T cells isolated from vaccinated mice demonstrates that peptides with mutated residues, but not the wild-type residues, are recognized. Immunization of these peptides revealed that a CD4 repertoire exists for the mutated peptides but is lacking for the wild-type peptides and that the mutated residues are processed, loaded, and presented on the I-A(b) molecule. Overall, our results illustrate that, although autoantibodies are generated against the endogenous protein, CD4 cells are activated through a neo-epitope recognition mechanism. Therefore, tolerance is maintained at a CD4 level but is broken at the level of antibody production. Finally, these results suggest that naturally occurring posttranslational modifications such as nitration may play a role in antibody-mediated autoimmune disorders.

Topics: Amino Acid Substitution; Amino Acids; Animals; Autoantibodies; CD4-Positive T-Lymphocytes; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Epitopes; Female; Immune Tolerance; Immunization; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Mutant Proteins; Phenylalanine; Time Factors; Tumor Necrosis Factor-alpha; Tyrosine

2011