T cell receptor gene usage in desmoglein-3-specific T lymphocytes from patients with pemphigus vulgaris.
Pemphigus vulgaris (PV) is an autoimmune disease mediated by autoantibodies against desmoglein-3 (Dsg3). It has been documented that both humoral and cellular autoimmunity play essential roles in the development of PV. Recently, we identified that T cells from PV patients respond to three antigenic fragments on the ectodomain of Dsg3. These T cells are CD4 alpha/beta cells secreting a Th2-like cytokine profile, and responding of Dsg3 in a restriction to HLA-DRBI*0402 or 1401 alleles. Other characteristics of these cells, such as detailed epitope(s) and T cell receptors (TCRs) usage, however, have not been investigated. The purpose of this study is to determine detailed T cell epitope(s) and TCR genes utilized by Dsg3-specific T cells. Here, we found that Dsg3(AA145-192)-specific cells preferentially utilize the TCRVbeta13 gene, while Dsg3(AA240-303)- and Dsg3 (AA570-614)-specific cells utilize Vbeta7 and Vbeta17 genes, respectively. Analysis of TCRValpha gene expression, it appears that Valpha22 gene is expressed by Dsg3(AA145-192)-specific cells, whereas the Valpha10 gene is predominantly utilized by Dsg3(AA240-303)-specific T cells. There are no specific utilization of Valpha gene in the group of cells proliferate to Dsg3 (AA570-614). We believe that this information will further our understanding of the properties of autoimmune T cells in patients with PV.
Hacker-Foegen
Mary K
MK
Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Fairley
Janet A
JA
Lin
Mong-Shang
MS
D000595:Amino Acid Sequence; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D015820:Cadherins / Q000235:genetics* / Q000276:immunology*; D002999:Clone Cells; D051184:Desmoglein 3; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D006801:Humans; D010392:Pemphigus / Q000235:genetics* / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology
D015820:Cadherins; C071894:DSG3 protein, human; D051184:Desmoglein 3; D018984:Epitopes, T-Lymphocyte; D011948:Receptors, Antigen, T-Cell