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

S. L. Karp, T. Kieber-Emmons, Jane Sun Mae Jane Sun, G. Wolf, E. G. Neilson

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

The autoimmune B cell repertoire in anti-tubular basement membrane (αTBM) 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 αTBM/α3M-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 α3M-1 antibodies is derived from several recurring germ-line V(H) 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.

Original languageEnglish (US)
Pages (from-to)867-879
Number of pages13
JournalJournal of Immunology
Volume150
Issue number3
StatePublished - Jan 1 1993
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Karp, S. L., Kieber-Emmons, T., Mae Jane Sun, J. S., Wolf, G., & Neilson, E. G. (1993). Molecular structure of a cross-reactive idiotype on autoantibodies recognizing parenchymal self. Journal of Immunology, 150(3), 867-879.