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Dual T cell receptor T cells with two defined specificities mediate tumor suppression via both receptors

Item Type:Article
Title:Dual T cell receptor T cells with two defined specificities mediate tumor suppression via both receptors
Creators Name:Gladow, M. and Uckert, W. and Blankenstein, T.
Abstract:Grafting T cells with new antigen specificity by T cell receptor (TCR) gene transfer could greatly facilitate adoptive T cell immunotherapy. Little is known about how two TCR on one T cell influence each other. Among other reasons, this is often due to the fact that only one TCR specificity is known. We have genetically generated murine dual TCR T cells (OT-I/P14), specific for ovalbumin (ova257) and lymphocyte choriomeningitis virus glycoprotein (gp33). These cells retain both specificities and can be stimulated by either antigenic peptide to proliferate and produce IFN-γ. Even though one TCR (P14) is expressed at reduced levels on dual TCR T cells, the peptide sensitivity of these cells is similar to that of single TCR T cells of the same specificity. TCR down-modulation on dual TCR T cells depends primarily on binding of the specific ligand. Adoptively transferred dual TCR T cells suppress the growth of both B16-ova and B16-gp33 melanoma cells, regardless of the peptide used for in vitro activation. Taken together, despite a certain dominance of expression between two TCR on the same T cell, this need not necessarily have functional consequences.
Keywords:Adoptive Immunotherapy, Dual TCR Transgenic Mice, Tumor, Animals, Chickens, Mice
Source:European Journal of Immunology
ISSN:0014-2980
Publisher:Wiley (U.S.A.)
Volume:34
Number:7
Page Range:1882-1891
Date:1 July 2004
Official Publication:https://doi.org/10.1002/eji.200425041
PubMed:View item in PubMed

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