Identification and characterization of autoreactive T cell responses to bullous pemphigoid antigen 2 in patients and healthy controls

Lioba Büdinger, Luca Borradori, Carole Yee, Rüdiger Eming, Stanislav Ferencik, Hans Grosse-Wilde, Hans F. Merk, Kim Yancey, Michael Hertl

Research output: Contribution to journalArticle

169 Scopus citations

Abstract

Antibodies against the extracellular domain of bullous pemphigoid antigen 2 (BPAG2) are thought to play a key role in the pathogenesis of bullous pemphigoid (BP), the most frequent autoimmune bullous disease of the skin. Autoreactive T cell responses to BPAG2 were investigated in 16 BP patients and 24 healthy controls by coculture of PBMC with two recombinant BPAG2 proteins (extracellular domain of BPAG2). Primary in vitro T cell responses to BPAG2 were observed in 10/12 BP patients expressing the BP- associated HLA-DQB1*0301 allele and 8/10 DQB1*0301 positive healthy individuals. DQB1*0301 also restricted three autoreactive T cell lines from two BP patients and a healthy donor. In contrast, PBMC from 14 normal patients carrying HLA class II alleles other than DQB1*0301 were not stimulated by BPAG2. Autoreactive BPAG2-specific CD4+ T cell lines and clones from five BP patients produced both Th1 and Th2 cytokines, whereas three autoreactive T cell lines from three DQB1*0301 positive normal patients produced exclusively IFN-γ. The absence of BPAG2-specific Th2 cells in healthy individuals strongly suggests that autoreactive Th2 responses to BPAG2 are restricted to BP patients and may thus be critical in the pathogenesis of BP.

Original languageEnglish (US)
Pages (from-to)2082-2089
Number of pages8
JournalJournal of Clinical Investigation
Volume102
Issue number12
DOIs
StatePublished - Dec 15 1998

Keywords

  • Autoreactive Th1/Th2 cells
  • Cytokines
  • Extracellular domain
  • HLA class II restriction
  • Hemidesmosome

ASJC Scopus subject areas

  • Medicine(all)

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