Conformational epitope mapping of antibodies against desmoglein 3 in experimental murine pemphigus vulgaris

Hidemi Anzai, Yoshiko Fujii, Koji Nishifuji, Miyo Aoki-Ota, Takayuki Ota, Masayuki Amagai, Takeji Nishikawa

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background: Pemphigus vulgaris (PV) is a blistering skin disease caused by IgG autoantibodies against desmoglein 3 (Dsg3). We have recently developed an active disease mouse model for PV by adoptive transfer of splenocytes from immunized or naive Dsg3-/- mice into Rag2-/- recipient mice. Objective: In this study, we characterized the conformational epitopes of anti-Dsg3 IgG antibodies and their pathogenic activities in the PV model mice. Methods: The binding regions of anti-Dsg3 IgG antibodies were assessed by competition ELISAs with domain-swapped mouse Dsg1/Dsg3 molecules in PV model mice receiving immunized (n = 53) or naive (n = 56) splenocytes. To compare the pathogenic activity of antibodies against N-terminal versus C-terminal extracellular domains, Dsg3-/- mice were immunized with the residues 1-162 or the residues 403-565 of mouse Dsg3, and the splenocytes were adoptively transferred into Rag2-/- mice. Results: The middle to C-terminal extracellular domains of Dsg3 (residues 195-565) showed >50% competition in 51/53 (96.2%) and 45/56 (80.4%) while the N-terminal domain (residues 1-162) showed >50% competition only in 3/53 (5.7%) and 8/56 (14.3%) in mice receiving immunized and naive splenocytes, respectively. The mice receiving Dsg3-/- splenocytes immunized with the residues 403-565 developed the PV phenotype as early as and as severely as the mice receiving splenocytes immunized with the residues 1-162. Conclusions: In PV model mice the antibodies were dominantly raised against the middle to C-terminal extracellular domains of mouse Dsg3 where amino acid sequences are less conserved among desmoglein isoforms and that those antibodies may also be involved in the blister formation.

Original languageEnglish
Pages (from-to)133-142
Number of pages10
JournalJournal of Dermatological Science
Volume35
Issue number2
DOIs
Publication statusPublished - 2004 Aug 1

Keywords

  • Autoimmune
  • Cadherin
  • Cell adhesion
  • Desmosomes
  • Dsg1
  • Dsg3
  • PV
  • desmoglein 1
  • desmoglein 3
  • mDsg1
  • mDsg3
  • mouse desmoglein 1
  • mouse desmoglein 3
  • pemphigus vulgaris

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

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