Reference - Detail
|Author||Tsujihata Y, So T, Chijiiwa Y, Hashimoto Y, Hirata M, Ueda T, Imoto T.|
|Title||Mutant mouse lysozyme carrying a minimal T cell epitope of hen egg lysozyme evokes high autoantibody response.|
Self proteins including foreign T cell epitope induce autoantibodies. We evaluated the relationship between the size of foreign Ag introduced into self protein and the magnitude of autoantibody production. Mouse lysozyme (ML) was used as a model self protein, and we prepared three different ML derivatives carrying T cell epitope of hen egg white lysozyme (HEL) 107-116, i.e, heterodimer of ML and HEL (ML-HEL), chimeric lysozyme that has residue 1-82 of ML and residue 83-130 of HEL in its sequence (chiMH), and mutant ML that has triple mutations rendering the most potent T cell epitope of HEL (sequence 107-116). Immunization of BALB/c mice with these three ML derivatives induced anti-ML autoantibody responses, whereas native ML induced no detectable response. In particular, mutML generated a 10(4) times higher autoantibody titer than did ML-HEL. Anti-HEL107-116 T cell-priming activities were almost similar among the ML derivatives. The heterodimerization of mutant ML and HEL led to significant reduction of the autoantibody response, whereas the mixture did not. These results show that size of the nonself region in modified self Ag has an important role in determining the magnitude of the autoantibody response, and that decrease in the foreign region in a modified self protein may cause high-titered autoantibody response.
|MeSH||Animals Autoantibodies / biosynthesis* Autoantibodies / metabolism Binding Sites, Antibody Chickens Dose-Response Relationship, Immunologic Enzyme-Linked Immunosorbent Assay Epitopes, T-Lymphocyte / administration & dosage Epitopes, T-Lymphocyte / genetics* Epitopes, T-Lymphocyte / immunology* Epitopes, T-Lymphocyte / metabolism Female Immunoglobulin G / biosynthesis Immunoglobulin G / metabolism Injections, Subcutaneous Lymphocyte Activation / genetics Male Mice Mice, Inbred BALB C Mice, Inbred C3H Mice, Inbred C57BL Muramidase / administration & dosage Muramidase / genetics* Muramidase / immunology* Ovum / immunology* Peptide Fragments / administration & dosage Peptide Fragments / genetics* Peptide Fragments / immunology* Recombinant Fusion Proteins / administration & dosage Recombinant Fusion Proteins / immunology Recombinant Proteins / administration & dosage Recombinant Proteins / immunology T-Lymphocytes / immunology|
|Human and Animal Cells|