Molecular structure of a cross-reactive idiotype on autoantibodies recognizing parenchymal self
| Autor: | S L Karp, T Kieber-Emmons, M J Sun, G Wolf, E G Neilson |
|---|---|
| Rok vydání: | 1993 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 150:867-879 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.150.3.867 |
| Popis: | The autoimmune B cell repertoire in anti-tubular basement membrane (alpha TBM) disease is focused on the nephritogenic P1 domain of the 3M-1 target Ag in kidney and normally expresses a disease-modifying cross-reactive Id (IdX). The molecular structure of this Id was determined from a library of rat mAb alpha TBM/alpha 3M-1 by using anchor polymerase chain reactions. Our findings provide the first alignment of V region sequences for rat IgG and reveal that specificity for the P1 domain among alpha 3M-1 antibodies is derived from several recurring germ-line VH genes which have not undergone somatic mutation. The IdX in this repertoire localizes to the H chain on Western blot, and to the CDR3 region as deduced from the cDNA encoding several informative clones. Computer modeling of the Id reveals a conformational structure largely dependent on hydroxyl groups in or near turn position 4 of the H chain CDR3 region. These findings demonstrate that regulatory elements protective of autoimmunity are not encoded in the germ line as IdX, but rather emerge from a recombinatorial diversity engaged by the recognition of parenchymal self. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|