Heterogeneous MHC II restriction pattern of autoreactive desmoglein 3 specific T cell responses in pemphigus vulgaris patients and normals

M. Hertl, R. W. Karr, Masayuki Amagai, S. I. Katz

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Pemphigus vulgaris is a life threatening bullous autoimmune disease of the skin mediated by autoantibodies against desmoglein 3 (Dsg3) on epidermal keratinocytes. Pemphigus vulgaris patients exhibit T cell responses against Dsg3 that may serve as a target to modulate the production of pathogenic autoantibodies. Healthy carriers of major histocompatibility complex class II alleles identical or similar to those that are highly prevalent in pemphigus vulgaris, namely DRβ1*0402 and DRβ1*1401, also mount T cell responses against Dsg3. We thus wanted to determine whether these prevalent major histocompatibility complex class II alleles restricted Dsg3 specific T cell responses. A CD4+ T cell line from the DRβ1*0402+ patient PV9 was stimulated by Dsg3 with DRβ1*0402+ L cells as antigen-presenting cells. A CD4+ T cell line and six CD4+ T cell clones from the DR11/14+ patient PV8, and six CD4+ T cell clones from the DR11+ healthy donor C6, required DR11/ DQβ1*0301+ peripheral blood mononuclear cells but not DR11+ L cells as antigen-presenting cells and were strongly inhibited by anti-DQ antibodies, indicating that they were restricted by HLA-DQβ1*0301. A CD4+ T cell line and three T cell clones from the DR11+ healthy donor C11 were differentially stimulated by Dsg3 with L cells expressing one of several DR11 alleles. T cell recognition of Dsg3 was thus not only restricted by the pemphigus vulgaris associated DRβ1*0402 allele, but also by several DR11 alleles, some of which are highly homologous to DRβ1*0402, and by HLA-DQβ1*0301.

Original languageEnglish
Pages (from-to)388-392
Number of pages5
JournalJournal of Investigative Dermatology
Volume110
Issue number4
DOIs
Publication statusPublished - 1998
Externally publishedYes

Fingerprint

Desmoglein 3
Pemphigus
T-cells
T-Lymphocytes
Alleles
Clone Cells
Antigen-Presenting Cells
Major Histocompatibility Complex
Cell Line
Autoantibodies
Tissue Donors
Vesiculobullous Skin Diseases
Keratinocytes
Autoimmune Diseases
Anti-Idiotypic Antibodies
Blood Cells
Skin
Blood

Keywords

  • Autoreactivity
  • Desmosome
  • MHC II
  • T lymphocytes

ASJC Scopus subject areas

  • Dermatology

Cite this

Heterogeneous MHC II restriction pattern of autoreactive desmoglein 3 specific T cell responses in pemphigus vulgaris patients and normals. / Hertl, M.; Karr, R. W.; Amagai, Masayuki; Katz, S. I.

In: Journal of Investigative Dermatology, Vol. 110, No. 4, 1998, p. 388-392.

Research output: Contribution to journalArticle

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AB - Pemphigus vulgaris is a life threatening bullous autoimmune disease of the skin mediated by autoantibodies against desmoglein 3 (Dsg3) on epidermal keratinocytes. Pemphigus vulgaris patients exhibit T cell responses against Dsg3 that may serve as a target to modulate the production of pathogenic autoantibodies. Healthy carriers of major histocompatibility complex class II alleles identical or similar to those that are highly prevalent in pemphigus vulgaris, namely DRβ1*0402 and DRβ1*1401, also mount T cell responses against Dsg3. We thus wanted to determine whether these prevalent major histocompatibility complex class II alleles restricted Dsg3 specific T cell responses. A CD4+ T cell line from the DRβ1*0402+ patient PV9 was stimulated by Dsg3 with DRβ1*0402+ L cells as antigen-presenting cells. A CD4+ T cell line and six CD4+ T cell clones from the DR11/14+ patient PV8, and six CD4+ T cell clones from the DR11+ healthy donor C6, required DR11/ DQβ1*0301+ peripheral blood mononuclear cells but not DR11+ L cells as antigen-presenting cells and were strongly inhibited by anti-DQ antibodies, indicating that they were restricted by HLA-DQβ1*0301. A CD4+ T cell line and three T cell clones from the DR11+ healthy donor C11 were differentially stimulated by Dsg3 with L cells expressing one of several DR11 alleles. T cell recognition of Dsg3 was thus not only restricted by the pemphigus vulgaris associated DRβ1*0402 allele, but also by several DR11 alleles, some of which are highly homologous to DRβ1*0402, and by HLA-DQβ1*0301.

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