Recognition of Desmoglein 3 by Autoreactive T Cells in Pemphigus Vulgaris Patients and Normals

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 (DN1), 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.