Molecular characterization of a major nephritogenic domain in the autoantigen of anti-tubular basement membrane disease
| Autor: | Carolyn J. Kelly, William H. Hines, Thomas P. Haverty, Nancy E. Cooke, M D Clayman, Mae Jane Sun, Eric G. Neilson |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Databases
Factual T-Lymphocytes Molecular Sequence Data Restriction Mapping Protein domain Mice Inbred Strains Biology Lymphocyte Activation Autoantigens Immunotherapy Adoptive Antibodies Basement Membrane Epitope Mice Immune system Antigen Sequence Homology Nucleic Acid medicine Animals Amino Acid Sequence RNA Messenger Peptide sequence Gene Library chemistry.chemical_classification Basement membrane Multidisciplinary Nucleic Acid Hybridization Blotting Northern Molecular biology Rats Kidney Tubules medicine.anatomical_structure chemistry Rats Inbred Lew biology.protein Nephritis Interstitial Antibody Peptides Glycoprotein Research Article |
| Zdroj: | Proceedings of the National Academy of Sciences. 88:2006-2010 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.88.5.2006 |
| Popis: | Anti-tubular basement membrane (alpha TBM) disease is a form of primary interstitial nephritis mediated by autoimmune T cells and alpha TBM antibodies. In mice and humans the nephritogenic immune response is directed to a glycoprotein (3M-1) found along the proximal tubule of the kidney. We have isolated cDNAs from an expression library that encodes for the common framework domain of the 3M-1 antigen. This common domain was once related evolutionarily to a family of intermediate filament-associated proteins. Northern hybridization revealed that all isoforms of 3M-1 range between 1700 and 1900 base pairs and in situ hybridization studies indicate that transcripts are found in tubular epithelium. Candidate peptide fragments were deduced and synthesized from the sequence encoding this common framework domain, and one of the peptide residues was able to bind a monoclonal 3M-1-reactive alpha TBM antibody, stimulate the growth of 3M-1-reactive helper T cells, and induce nephritogenic effector T cells capable of producing interstitial nephritis. Our results indicate that a unique, immunodominant region of the 3M-1 antigen is an informative participant in the emergence of autoimmune injury to certain basement membranes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|