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

166 Citations (Scopus)

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
StatePublished - Dec 15 1998

Fingerprint

Bullous Pemphigoid
T-Lymphocytes
Antigens
Cell Line
Alleles
Th2 Cells

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Büdinger, L., Borradori, L., Yee, C., Eming, R., Ferencik, S., Grosse-Wilde, H., ... Hertl, M. (1998). Identification and characterization of autoreactive T cell responses to bullous pemphigoid antigen 2 in patients and healthy controls. Journal of Clinical Investigation, 102(12), 2082-2089.

Identification and characterization of autoreactive T cell responses to bullous pemphigoid antigen 2 in patients and healthy controls. / Büdinger, Lioba; Borradori, Luca; Yee, Carole; Eming, Rüdiger; Ferencik, Stanislav; Grosse-Wilde, Hans; Merk, Hans F.; Yancey, Kim; Hertl, Michael.

In: Journal of Clinical Investigation, Vol. 102, No. 12, 15.12.1998, p. 2082-2089.

Research output: Contribution to journalArticle

Büdinger, L, Borradori, L, Yee, C, Eming, R, Ferencik, S, Grosse-Wilde, H, Merk, HF, Yancey, K & Hertl, M 1998, 'Identification and characterization of autoreactive T cell responses to bullous pemphigoid antigen 2 in patients and healthy controls', Journal of Clinical Investigation, vol. 102, no. 12, pp. 2082-2089.
Büdinger, Lioba ; Borradori, Luca ; Yee, Carole ; Eming, Rüdiger ; Ferencik, Stanislav ; Grosse-Wilde, Hans ; Merk, Hans F. ; Yancey, Kim ; Hertl, Michael. / Identification and characterization of autoreactive T cell responses to bullous pemphigoid antigen 2 in patients and healthy controls. In: Journal of Clinical Investigation. 1998 ; Vol. 102, No. 12. pp. 2082-2089.
@article{157e1649fa6547598e4be11ada65e273,
title = "Identification and characterization of autoreactive T cell responses to bullous pemphigoid antigen 2 in patients and healthy controls",
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.",
keywords = "Autoreactive Th1/Th2 cells, Cytokines, Extracellular domain, Hemidesmosome, HLA class II restriction",
author = "Lioba B{\"u}dinger and Luca Borradori and Carole Yee and R{\"u}diger Eming and Stanislav Ferencik and Hans Grosse-Wilde and Merk, {Hans F.} and Kim Yancey and Michael Hertl",
year = "1998",
month = "12",
day = "15",
language = "English (US)",
volume = "102",
pages = "2082--2089",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "12",

}

TY - JOUR

T1 - Identification and characterization of autoreactive T cell responses to bullous pemphigoid antigen 2 in patients and healthy controls

AU - Büdinger, Lioba

AU - Borradori, Luca

AU - Yee, Carole

AU - Eming, Rüdiger

AU - Ferencik, Stanislav

AU - Grosse-Wilde, Hans

AU - Merk, Hans F.

AU - Yancey, Kim

AU - Hertl, Michael

PY - 1998/12/15

Y1 - 1998/12/15

N2 - 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.

AB - 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.

KW - Autoreactive Th1/Th2 cells

KW - Cytokines

KW - Extracellular domain

KW - Hemidesmosome

KW - HLA class II restriction

UR - http://www.scopus.com/inward/record.url?scp=0032535445&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032535445&partnerID=8YFLogxK

M3 - Article

C2 - 9854043

AN - SCOPUS:0032535445

VL - 102

SP - 2082

EP - 2089

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 12

ER -