title: Recognition of desmoglein 3 by autoreactive T cells in pemphigus vulgaris patients and normals.
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 degrees) or tertiary (3 degrees) T cell responses to Dsg3. T cell responses to Dsg3 were also observed in four of 12 healthy individuals upon 2 degrees or 3 degrees stimulation with Dsg3. Both PV patients and healthy responders were either positive for DRbeta1*0402 -- which is highly prevalent in PV -- or positive for DR11 alleles homologous to DRbeta1*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 (deltaN1), 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.
authors.affiliation: Dermatology Branch, National Cancer Institute, Bethesda, Maryland, USA.
authors.forename: M
authors.initials: M
authors.lastname: Hertl
authors.forename: M
authors.initials: M
authors.lastname: Amagai
authors.forename: H
authors.initials: H
authors.lastname: Sundaram
authors.forename: J
authors.initials: J
authors.lastname: Stanley
authors.forename: K
authors.initials: K
authors.lastname: Ishii
authors.forename: S I
authors.initials: SI
authors.lastname: Katz
mesh_terms: D000918:Antibody Specificity; D001324:Autoantigens / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015820:Cadherins / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D051184:Desmoglein 3; D000939:Epitopes; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D010392:Pemphigus / Q000097:blood*; D011994:Recombinant Proteins / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology / Q000494:pharmacology
chemical_list: D001324:Autoantigens; D015820:Cadherins; D016207:Cytokines; C071894:DSG3 protein, human; D051184:Desmoglein 3; D000939:Epitopes; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D011994:Recombinant Proteins; D013745:Tetanus Toxoid