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Blood, 1 January 2007, Vol. 109, No. 1, pp. 235-243. Prepublished online as a Blood First Edition Paper on September 12, 2006; DOI 10.1182/blood-2006-03-013318. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-03-013318v1 109/1/235    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Heemskerk, M. H. M. Articles by Falkenburg, J. H. F. Search for Related Content PubMed PubMed Citation Articles by Heemskerk, M. H. M. Articles by Falkenburg, J. H. F. Related Collections Immunobiology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Efficiency of T-cell receptor expression in dual-specific T cells is controlled by the intrinsic qualities of the TCR chains within the TCR-CD3 complex Mirjam H. M. Heemskerk1,, Renate S. Hagedoorn1, Menno A. W. G. van der Hoorn1, Lars T. van der Veken1, Manja Hoogeboom1, Michel G. D. Kester1, Roel Willemze1, and J. H. Frederik Falkenburg1 1 Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands Genetic engineering of T lymphocytes is an attractive strategy to specifically redirect T-cell immunity toward viral infections and malignancies. We previously demonstrated redirected antileukemic reactivity of cytomegalovirus (CMV)–specific T cells by transfer of minor histocompatibility antigen HA-2–specific T-cell receptors (TCRs). HA-2–TCR-transferred CMV-specific T cells were potent effectors against HA-2–expressing leukemic cells, as well as CMV-expressing cells. Functional activity of these T cells correlated with TCR cell-surface expression. In the present study we analyzed which properties of transferred and endogenous TCRs are crucial for efficient cell-surface expression. We demonstrate that expression of the introduced TCR is not a random process but is determined by characteristics of both the introduced and the endogenously expressed TCR. The efficiency of TCR cell-surface expression is controlled by the intrinsic quality of the TCR complex. In addition, we demonstrate that chimeric TCRs can be formed and that efficiency of TCR expression is independent of whether TCRs are retrovirally introduced or naturally expressed. In conclusion, introduced, endogenous, and chimeric TCRs compete for cell-surface expression in favor of the TCR-CD3 complex with best-pairing properties. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Monogamy and polygamy in T-cell receptor (TCR) chain association Terrence L. Geiger Blood 2007 109: 5-6. [Full Text] [PDF] This article has been cited by other articles: M. Griffioen, H.M. E. van Egmond, H. Barnby-Porritt, M. A.W.G. van der Hoorn, R. S. Hagedoorn, M. G.D. Kester, N. Schwabe, R. Willemze, J.H. F. Falkenburg, and M. H.M. Heemskerk Genetic engineering of virus-specific T cells with T-cell receptors recognizing minor histocompatibility antigens for clinical application Haematologica, October 1, 2008; 93(10): 1535 - 1543. [Abstract] [Full Text] [PDF] Z. Sebestyen, E. Schooten, T. Sals, I. Zaldivar, E. San Jose, B. Alarcon, S. Bobisse, A. Rosato, J. Szollosi, J. W. Gratama, et al. Human TCR That Incorporate CD3{zeta} Induce Highly Preferred Pairing between TCR{alpha} and {beta} Chains following Gene Transfer J. Immunol., June 1, 2008; 180(11): 7736 - 7746. 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Selecting highly affine and well-expressed TCRs for gene therapy of melanoma Blood, November 15, 2007; 110(10): 3564 - 3572. [Abstract] [Full Text] [PDF] S. Thomas, S.-A. Xue, M. Cesco-Gaspere, E. San Jose, D. P. Hart, V. Wong, R. Debets, B. Alarcon, E. Morris, and H. J. Stauss Targeting the Wilms Tumor Antigen 1 by TCR Gene Transfer: TCR Variants Improve Tetramer Binding but Not the Function of Gene Modified Human T Cells J. Immunol., November 1, 2007; 179(9): 5803 - 5810. [Abstract] [Full Text] [PDF] A. U. van Lent, M. Nagasawa, M. M. van Loenen, R. Schotte, T. N. M. Schumacher, M. H. M. Heemskerk, H. Spits, and N. Legrand Functional Human Antigen-Specific T Cells Produced In Vitro Using Retroviral T Cell Receptor Transfer into Hematopoietic Progenitors J. Immunol., October 15, 2007; 179(8): 4959 - 4968. [Abstract] [Full Text] [PDF] C. J. Cohen, Y. F. Li, M. El-Gamil, P. F. Robbins, S. A. Rosenberg, and R. A. 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