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

研究成果: Article査読

17 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)133-142
ページ数10
ジャーナルJournal of Dermatological Science
35
2
DOI
出版ステータスPublished - 2004 8

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 皮膚病学

フィンガープリント

「Conformational epitope mapping of antibodies against desmoglein 3 in experimental murine pemphigus vulgaris」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル