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.