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The Journal of Immunology, Vol 150, Issue 3 867-879, Copyright © 1993 by American Association of Immunologists

ARTICLES

Molecular structure of a cross-reactive idiotype on autoantibodies recognizing parenchymal self

SL Karp, T Kieber-Emmons, MJ Sun, G Wolf and EG Neilson
Renal-Electrolyte Divisions, University of Pennsylvania, Philadelphia 19104.

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.


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