Detection of low avidity desmoglein 3-reactive T cells in pemphigus vulgaris using HLA-DR beta 1*0402 tetramers.
In the present study, we developed a HLA class II tetramer-based detection system utilizing DRB1*0402 tetramers loaded with recently identified immunodominant peptides of desmoglein 3 (Dsg3), the major autoantigen of pemphigus vulgaris (PV). Initial experiments demonstrated staining of a Dsg3-reactive T cell hybridoma which was derived from HLA-DR0402-transgenic mice with loaded PE-labeled DRbeta1*0402 tetramers. However, staining of autoreactive T cell clones (TCC) derived from PV patients resulted only in positive staining by addition of exogenous peptides to the staining reactions. There was a dose-dependent specific binding of TCC to the tetramers with the agonistic Dsg3 peptide which was not altered by exogenous unrelated Dsg3 peptide. Noteworthy, the TCC did not stain with HLA-DR4 tetramers complexed with unrelated Dsg3 peptides. The findings of this study suggest that HLA class II tetramers may provide a highly specific approach to monitor ex vivo the T cellular autoimmune response against Dsg3 in patients with PV.
Veldman
Christian
C
Department of Dermatology and Allergology, University of Marburg, Deutschhausstrasse 9, D-35033 Marburg, Germany. veldman@med.uni-marburg.de
Eming
Rüdiger
R
Wolff-Franke
Sonja
S
Sonderstrup
Grete
G
Kwok
William W
WW
Hertl
Michael
M
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D002478:Cells, Cultured; D051184:Desmoglein 3 / Q000276:immunology* / Q000378:metabolism; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism*; D059811:HLA-DRB1 Chains; D006801:Humans; D006825:Hybridomas; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010392:Pemphigus / Q000276:immunology* / Q000473:pathology; D011485:Protein Binding / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
C071894:DSG3 protein, human; D051184:Desmoglein 3; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553506:HLA-DRB1*04:02 antigen