A restricted clonal T-cell receptor αβ repertoire in Sézary syndrome is indicative of superantigenic stimulation

Br J Dermatol. 2011 Jul;165(1):78-84. doi: 10.1111/j.1365-2133.2011.10308.x. Epub 2011 Jun 2.


Background: Sézary 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 Vβ8, Vβ13, Vβ17, Vβ21 and Vβ22, and under-representation of Vβ2 and Jβ1.1 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 Vα or Jα 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 Vβ and Jβ gene usage does seem to point to a restricted TCR repertoire, possibly as a result of superantigenic selection prior to neoplastic transformation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cells, Cultured
  • Cohort Studies
  • Female
  • Flow Cytometry
  • Humans
  • Male
  • Middle Aged
  • Receptors, Antigen, T-Cell, alpha-beta / analysis
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Sequence Analysis, DNA
  • Sezary Syndrome / immunology*
  • Skin Neoplasms / immunology*
  • Superantigens / immunology*
  • T-Lymphocytes / immunology*


  • Receptors, Antigen, T-Cell, alpha-beta
  • Superantigens