Strong induction of tyrosine phosphorylation, intracellular calcium, nuclear transcription factors and interferongamma, but weak induction of IL-2 in naïve T cells stimulated by bacterial superantigen.
The outcome of T cell receptor (TCR) engagement is controlled by the differential recruitment of a variety of pathways, depending on the nature of the TCR ligand. Studies on superantigens (SAGs) were among the first describing such differential signaling; however, reported results are inconsistent. We took a quantitative approach to reinvestigate this question. Using nai;ve T cells from TCR transgenic mice, we found that compared to the antigenic peptide from pigeon cytochrome c, the SAG staphylococcal enterotoxin A very efficiently (100-2000-fold more sensitive on a weight basis) induced tyrosine kinase activity, intracellular calcium increase, and interferon (IFN)gamma production. Up-regulation of CD25 and CD69 and proliferation were less efficiently induced (20-30-fold more sensitive), and interleukin (IL)-2 production was induced least efficiently (only 2-fold more sensitive). This differential activation profile that varies with the activation event analyzed is discussed with respect to the propensity for SAG to induce anergy.
Luxembourg
Alain
A
Division of Immunochemistry, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA. aluxembourg@ichorms.com
Grey
Howard
H
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D017635:Clonal Anergy; D003574:Cytochrome c Group; D004768:Enterotoxins / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis*; D037181:Lectins, C-Type; D051379:Mice; D008822:Mice, Transgenic; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000032:analysis; D018089:Superantigens / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis*; D014443:Tyrosine / Q000378:metabolism*; D015854:Up-Regulation; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D002118:Calcium; D003574:Cytochrome c Group; D004768:Enterotoxins; D007371:Interferon-gamma; D007376:Interleukin-2; D037181:Lectins, C-Type; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015375:Receptors, Interleukin-2; D018089:Superantigens; D014157:Transcription Factors; D014443:Tyrosine; D000099192:CD69 Antigens; C026066:enterotoxin A, Staphylococcal