Recognition of desmoglein 3 by autoreactive T cells in pemphigus vulgaris patients and normals

M. Hertl, M. Amagai, H. Sundaram, J. Stanley, Ken Ishii, S. I. Katz

Research output: Chapter in Book/Report/Conference proceedingChapter

95 Citations (Scopus)

Abstract

Pemphigus vulgaris (PV) is an autoimmune blistering disease of the skin and is caused by autoantibodies against desmoglein 3 (Dsg3) on epidermal keratinocytes. Because the production of autoantibodies is presumably T cell dependent, Dsg3-specific T cell reactivity was investigated in 14 PV patients and 12 healthy donors. Peripheral blood mononuclear cells from seven PV patients with active disease showed a primary in vitro response to a recombinant protein containing the extracellular portion (EC1-5) of Dsg3, whereas two of seven PV patients in remission or under immunosuppressive treatment exhibited only secondary (2°) or tertiary (3°) T cell responses to Dsg3. T cell responses to Dsg3 were also observed in four of 12 healthy individuals upon 2°or 3°stimulation with Dsg3. Both PV patients and healthy responders were either positive for DRβ1*0402 - which is highly prevalent in PV - or positive for DR11 alleles homologous to DRβ1*0402. Two CD4 + Dsg3-specific T cell lines and 12 T cell clones from two PV patients and two CD4 + T cell lines and eight T cell clones from two normals were also stimulated by a Dsg3 protein devoid of the EC2-3 (ΔN1), suggesting that epitopes were located in the EC1, EC4, and/or EC5. Using Dsg3 peptides, one immunodominant peptide (residues 161-177) was also identified in the EC2. These observations demonstrate that T cell responses to Dsg3 can be detected in PV patients and in healthy donors carrying major histocompatibility class II alleles identical or similar to those highly prevalent in PV.

Original languageEnglish
Title of host publicationJournal of Investigative Dermatology
PublisherNature Publishing Group
Pages62-66
Number of pages5
Volume110
Edition1
DOIs
Publication statusPublished - 1998 Jan 1
Externally publishedYes

Keywords

  • Autoimmunity
  • Peptides
  • T lymphocytes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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    Hertl, M., Amagai, M., Sundaram, H., Stanley, J., Ishii, K., & Katz, S. I. (1998). Recognition of desmoglein 3 by autoreactive T cells in pemphigus vulgaris patients and normals. In Journal of Investigative Dermatology (1 ed., Vol. 110, pp. 62-66). Nature Publishing Group. https://doi.org/10.1046/j.1523-1747.1998.00086.x