Induction of peripheral tolerance in dual TCR T cells: an evidence for non-dominant signaling by one TCR.
Recently, the existence of T cells with dual T cell receptor (TCR) in the immune system is generally accepted, while it has been controversial whether signals through one TCR would affect the functions of the other. In this study T cells expressing two different TCR were obtained from cross-hybrids of LCMV and AND TCR transgenic mice specific for the gp33 and peptide fragment of PCC (fPCC), respectively. Peptide stimulation demonstrated that the dual TCR T cells functioned independently in an antigen-specific manner. To examine whether the tolerance targeted for the one TCR affects the responsiveness of the other, the cross-hybrids were treated with gp33. Although T cells from F1 mice were rendered anergenic to gp33, no functional changes to fPCC were observed in terms of cellular proliferation and IL-2 secretion, suggesting that the dual TCR T cells remained reactive to fPCC. We therefore propose that signaling through the TCR is receptor-specific and 'negative dominance' of one TCR by tolerance induction is not applicable in this dual TCR system.
Hah
Chaerim
C
Division of Molecular Life Sciences and College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea.
Kim
Mihyung
M
Kim
Kilhyoun
K
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018929:Cell Culture Techniques; D003433:Crosses, Genetic; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000032:analysis; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000382:microbiology*
D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell