Dual T cell receptor T cells with two defined specificities mediate tumor suppression via both receptors.
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-gamma. 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.
Gladow
Monika
M
Institute of Biology, Humboldt University Berlin, Berlin, Germany.
Uckert
Wolfgang
W
Blankenstein
Thomas
T
D019264:Adoptive Transfer; D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D002645:Chickens; D015536:Down-Regulation; D016654:Genes, RAG-1 / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010455:Peptides / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013379:Substrate Specificity; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D015854:Up-Regulation
D015395:Histocompatibility Antigens Class I; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma; D010047:Ovalbumin