A restricted clonal T-cell receptor alphabeta repertoire in Sezary syndrome is indicative of superantigenic stimulation.

摘要

BACKGROUND: Sezary syndrome (SS) is a cutaneous T-cell lymphoma characterized by erythroderma, lymphadenopathy and malignant clonal T cells in the skin, lymph nodes and peripheral blood. A role for superantigens in the pathogenesis of SS has been postulated before. OBJECTIVES: To investigate a putative involvement of chronic (super-)antigenic stimulation in driving T-cell expansion in SS. METHODS: Antigenic specificity of the T-cell receptor (TCR) was assayed by molecular analysis of the TCRA (n=11) and TCRB (n=28) genes, followed by detailed in silico analysis. RESULTS: Sequence analysis of clonally rearranged TCRB genes showed over-representation of Vbeta8, Vbeta13, Vbeta17, Vbeta21 and Vbeta22, and under-representation of Vbeta2 and Jbeta1.1 when compared with healthy controls. No similarity was detected in amino acid motifs of the complementarity determining region 3 (CDR3). Analysis of TCRA rearrangements showed that there was no common Valpha or Jalpha gene usage, and that TCRA CDR3 amino acid motifs were not highly similar. CONCLUSIONS: The lack of clear stereotypic TCRA and TCRB CDR3 amino acid motifs would argue against involvement of a single common antigen in the pathogenesis of SS. Nevertheless, the skewing of Vbeta and Jbeta gene usage does seem to point to a restricted TCR repertoire, possibly as a result of superantigenic selection prior to neoplastic transformation.