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

J Clin Invest. 1998 Dec 15;102(12):2082-9. doi: 10.1172/JCI3335.


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-gamma. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Autoantigens / immunology*
  • Autoimmune Diseases / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • Carrier Proteins*
  • Cell Division / immunology
  • Cells, Cultured
  • Clone Cells / immunology
  • Collagen / immunology*
  • Collagen Type XVII
  • Cytokines / immunology
  • Cytoskeletal Proteins*
  • Dystonin
  • Flow Cytometry
  • HLA-DQ Antigens / immunology
  • HLA-DQ beta-Chains
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • Middle Aged
  • Nerve Tissue Proteins*
  • Non-Fibrillar Collagens*
  • Pemphigoid, Bullous / immunology*
  • Recombinant Proteins / immunology
  • Skin / immunology*
  • T-Lymphocytes / immunology*
  • Th1 Cells / immunology
  • Th2 Cells / immunology


  • Autoantigens
  • Carrier Proteins
  • Cytokines
  • Cytoskeletal Proteins
  • DST protein, human
  • Dystonin
  • HLA-DQ Antigens
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • Histocompatibility Antigens Class II
  • Nerve Tissue Proteins
  • Non-Fibrillar Collagens
  • Recombinant Proteins
  • Collagen