T cell recognition of desmoglein 3 peptides in patients with pemphigus vulgaris and healthy individuals.
Pemphigus vulgaris is a severe autoimmune disease caused by autoantibodies against the cutaneous adhesion molecule, desmoglein 3 (Dsg3). The aim of this study was to characterize the specificity of autoreactive Th cells, which presumably regulate Dsg3-specific autoantibody production. Ninety-seven Th1 and Th2 clones isolated from 16 pemphigus patients and 12 HLA-matched healthy donors recognized the Dsg3 peptides, DG3(78-94), DG3(96-112), DG3(189-205), DG3(205-221), and DG3(250-266). Peptide DG3(96-112), and to a lesser extent DG3(250-266), was recognized by the majority of T cells from patients and healthy donors in association with HLA-DRB1*0402 and DQB1*0503 which were prevalent in the pemphigus patients and Dsg3-responsive healthy donors. Analyzing the Vbeta-chain of the TCR of the DG3(96-112)-specific T cells showed no restricted TCR usage. Peptides DG3(342-358) and DG3(376-392) were exclusively recognized by T cell clones (n=13) from patients while DG3(483-499) was only recognized by T cell clones (n=3) from a healthy donor. All Dsg3 peptides contained conserved amino acids at relative positions 1, 4, and 6; amino acids with a positive charge at position 4 presumably represent anchor motifs for DRB1*0402. These findings demonstrate that T cell recognition of distinct Dsg3 peptides is restricted by distinct HLA class II molecules and is independent from the development of pemphigus vulgaris.
Department of Dermatology, University of Erlangen-Nürnberg, Erlangen, Germany.
Christian M
CM
Veldman
Kerstin L
KL
Gebhard
Wolfgang
W
Uter
Ralf
R
Wassmuth
Joachim
J
Grötzinger
Erwin
E
Schultz
Michael
M
Hertl
D020816:Amino Acid Motifs / Q000276:immunology; D001324:Autoantigens / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism*; D002478:Cells, Cultured; D051184:Desmoglein 3; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism; D005110:Extracellular Space / Q000276:immunology / Q000378:metabolism; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006681:HLA-D Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D010392:Pemphigus / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism*; D010449:Peptide Mapping; D011485:Protein Binding / Q000276:immunology; D017434:Protein Structure, Tertiary; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D001324:Autoantigens; D015820:Cadherins; C071894:DSG3 protein, human; D051184:Desmoglein 3; D018984:Epitopes, T-Lymphocyte; D006681:HLA-D Antigens; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta