Molecular Structure of a Cross-Reactive Idiotype on Autoantibodies Recognizing Parenchymal Self

Sharon Karp, Thomas Kieber-Emmons, Mae Jane Sun, Gunter Wolf, Eric C. Neilson

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 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.

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

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Molecular Structure
Basement Membrane
Germ Cells
Autoantibodies
Autoimmunity
Hydroxyl Radical
Libraries
B-Lymphocytes
Complementary DNA
Clone Cells
Immunoglobulin G
Western Blotting
Kidney
Polymerase Chain Reaction
Mutation
Antibodies
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Karp, S., Kieber-Emmons, T., Sun, M. J., Wolf, G., & Neilson, E. C. (1993). Molecular Structure of a Cross-Reactive Idiotype on Autoantibodies Recognizing Parenchymal Self. Journal of Immunology, 150(3), 867-879.

Molecular Structure of a Cross-Reactive Idiotype on Autoantibodies Recognizing Parenchymal Self. / Karp, Sharon; Kieber-Emmons, Thomas; Sun, Mae Jane; Wolf, Gunter; Neilson, Eric C.

In: Journal of Immunology, Vol. 150, No. 3, 1993, p. 867-879.

Research output: Contribution to journalArticle

Karp, S, Kieber-Emmons, T, Sun, MJ, Wolf, G & Neilson, EC 1993, 'Molecular Structure of a Cross-Reactive Idiotype on Autoantibodies Recognizing Parenchymal Self', Journal of Immunology, vol. 150, no. 3, pp. 867-879.
Karp, Sharon ; Kieber-Emmons, Thomas ; Sun, Mae Jane ; Wolf, Gunter ; Neilson, Eric C. / Molecular Structure of a Cross-Reactive Idiotype on Autoantibodies Recognizing Parenchymal Self. In: Journal of Immunology. 1993 ; Vol. 150, No. 3. pp. 867-879.
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