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

J Immunol. 1993 Feb 1;150(3):867-79.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / genetics
  • Autoantibodies / chemistry
  • Autoantibodies / genetics*
  • Base Sequence
  • Basement Membrane / immunology
  • Chromosome Mapping
  • Computer Simulation
  • Cross Reactions
  • DNA / isolation & purification
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Idiotypes / chemistry
  • Immunoglobulin Idiotypes / genetics*
  • Immunoglobulin Variable Region / genetics
  • Kidney Tubules / immunology*
  • Molecular Sequence Data
  • Nephritis, Interstitial / immunology*
  • Protein Conformation
  • Rats

Substances

  • Antibodies, Monoclonal
  • Autoantibodies
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Idiotypes
  • Immunoglobulin Variable Region
  • DNA

Associated data

  • GENBANK/L07396
  • GENBANK/L07397
  • GENBANK/L07398
  • GENBANK/L07399
  • GENBANK/L07400
  • GENBANK/L07401
  • GENBANK/L07402
  • GENBANK/L07403
  • GENBANK/L07404
  • GENBANK/L07405
  • GENBANK/L07406
  • GENBANK/L07407
  • GENBANK/L07408
  • GENBANK/L07409
  • GENBANK/L07410
  • GENBANK/L07411
  • GENBANK/L07412