Staphylococcal enterotoxin-A directly stimulates signal transduction and interferon-gamma production in psoriatic T-cell lines

Tissue Antigens. 1998 Dec;52(6):530-8. doi: 10.1111/j.1399-0039.1998.tb03083.x.


Bacterial superantigens such as staphylococcal enterotoxin-A (SEA) have been implicated in the pathogenesis of psoriasis vulgaris. Major histocompatibility complex (MHC) class II molecules are high affinity receptors for SEA, and T cells found in psoriatic skin lesions express high levels of MHC class II. Here we address the question of whether SEA can directly activate psoriatic T cells in the absence of professional antigen-presenting cells. We show that SEA induces i) tyrosine phosphorylation of several proteins, ii) downregulation of the T-cell receptor (TCR), and iii) production of interferon-gamma (IFN-gamma), but not autocrine mitogenesis in CD8-positive T clones obtained from skin lesions of a patient with psoriasis vulgaris. Psoriatic T cells do not respond to SEA molecules if mutations are introduced in the TCRbeta- or in both the two MHC class II alpha- and beta-binding sites of SEA. Mutations in only one of the two MHC class II binding sites of SEA has different effects on T-cell activation. Thus, SEA molecules with a mutation in the MHC class II beta-binding site induce protein tyrosine phosphorylation, but not IFN-gamma production or co-stimulation of cytokine-mediated proliferation. In contrast, SEA with a mutation in the MHC class II alpha-binding site induces IFN-gamma and a qualitatively changed tyrosine phosphorylation profile. Both mutations delete the co-stimulatory effect on cytokine-mediated proliferation. This suggests that both MHC class II binding sites are involved in the autopresentation of SEA by psoriatic T cells. In conclusion, we provide evidence that SEA directly activates MVHC class H-positive psoriatic T-cell lines to produce IFN-gamma, a key cytokine in the pathogenesis of psoriasis vulgaris.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen-Presenting Cells
  • Binding Sites
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Line
  • Down-Regulation
  • Enterotoxins / immunology*
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • Interferon-gamma / biosynthesis*
  • Lymphocyte Activation
  • Phosphorylation
  • Psoriasis / immunology*
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Signal Transduction / immunology*
  • Tyrosine / metabolism


  • Enterotoxins
  • Histocompatibility Antigens Class II
  • Receptors, Antigen, T-Cell, alpha-beta
  • enterotoxin A, Staphylococcal
  • Tyrosine
  • Interferon-gamma