Molecular analysis of the autoantibody response in peptide-induced autoimmunity

Chaim Putterman, Bisram Deocharan, Betty Diamond

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Immunization of nonautoimmune BALB/c mice with multimeric DWEYSVWLSN, a peptide mimotope of DNA, induces anti-DNA and other lupus-associated Abs. To further investigate the pathogenesis of the autoantibody response induced by peptide immunization, we generated hybridomas from peptide-immunized mice that bound peptide, dsDNA, cardiolipin, Sm/ribonucleoprotein (RNP), or some combination of these Ags. Analysis of 24 IgM Abs led to the identification of three groups of Abs: 1) Abs reactive with peptide alone, 2) anti-peptide Abs cross-reactive with one or more autoantigens, and 3) autoantibodies that do not bind to peptide. The gene families and particular V(H)-V(L) combinations used in those hybridomas binding DNA were similar to those used in the anti- DNA response in spontaneous murine lupus. Another similarity to the spontaneous anti-DNA response was the generation of arginines in the complementarity-determining region-3 of DNA-binding hybridomas. Interestingly, one Ab had the V(H)-V(L) combination present in the original R4A anti-DNA Ab used to select the DWEYSVWLSN peptide from a phage display library. Many of the heavy and light chains displayed evidence of somatic mutation, suggesting that they were made by Ag-activated B cells. Analysis of the Ab repertoire in peptide-induced autoimmunity may provide insights into the generation of anti-DNA Abs following exposure to foreign Ag. Furthermore, the recovery of an Ab with the heavy and light chain combination of the Ab originally used to isolate the immunizing peptide confirms the utility of phage display peptide libraries in generating true molecular mimics.

Original languageEnglish (US)
Pages (from-to)2542-2549
Number of pages8
JournalJournal of Immunology
Volume164
Issue number5
StatePublished - Mar 1 2000

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Autoimmunity
Autoantibodies
Peptides
DNA
Hybridomas
Peptide Library
Immunization
Complementarity Determining Regions
Light
Social Identification
Cardiolipins
Ribonucleoproteins
Autoantigens
Immunoglobulin M
Arginine
B-Lymphocytes
Mutation
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Molecular analysis of the autoantibody response in peptide-induced autoimmunity. / Putterman, Chaim; Deocharan, Bisram; Diamond, Betty.

In: Journal of Immunology, Vol. 164, No. 5, 01.03.2000, p. 2542-2549.

Research output: Contribution to journalArticle

Putterman, Chaim ; Deocharan, Bisram ; Diamond, Betty. / Molecular analysis of the autoantibody response in peptide-induced autoimmunity. In: Journal of Immunology. 2000 ; Vol. 164, No. 5. pp. 2542-2549.
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