T cell receptor β chain gene usage in endemic pemphigus foliaceus (Fogo Selvagem)

The trimolecular complex comprised of the major histocompatibility complex, peptide antigen, and the T cell receptor is a requisite for T cell activation in normal and autoimmune responses. T cell receptor analysis is critical to further our understanding regarding mechanisms of T cell epitope selection and autoimmune initiation and progression and may help to identify targets for immunotherapy. Pemphigus foliaceus is an autoimmune blistering skin disease characterized by intraepidermal blisters and circulating autoantibodies directed against desmoglein 1, a 160 kDa transmembrane desmosomal molecule expressed in keratinocytes. As tissue damage is mediated by anti-desmoglein 1 antibodies, an initial T cell response is a likely requirement for autoantibody generation in this disease. To elucidate the role of pathogenic T cells in autoimmunity further, we have directly characterized the T cell receptor of T cells derived from pemphigus foliaceus patients. Complementary DNA was isolated from 17 desmoglein 1 specific T cell clones generated from pemphigus foliaceus patients by clonal expansion in vitro. To analyze the T cell repertoire, a panel of primers, collectively specific for the known human T cell receptor β variable region (TCRBV) families were paired with a constant region primer to polymerase chain reaction to amplify one distinct T cell receptor β variable region allele for each T cell clone studied. Polymerase chain reaction products were sequenced to determine exact β chain gene usage. In the 17 clones tested, 10 distinct T cell receptor β variable region usages and nine T cell receptor β joining gene segment usages were identified. Furthermore, T cell receptor β variable region and β joining usage did not appear to be random, but oligoclonal in nature, with some preference shown for T cell receptor β variable region 5S1 and T cell receptor BJ2S5.