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Blood, 15 June 2004, Vol. 103, No. 12, pp. 4613-4615. Prepublished online as a Blood First Edition Paper on February 26, 2004; DOI 10.1182/blood-2003-11-3903. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-11-3903v1 103/12/4613    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 Savage, P. Articles by Stauss, H. J. Search for Related Content PubMed PubMed Citation Articles by Savage, P. Articles by Stauss, H. J. Related Collections Immunobiology Neoplasia Transplantation Oncogenes and Tumor Suppressors Immunotherapy Brief Reports Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Brief report Use of B cell–bound HLA-A2 class I monomers to generate high-avidity, allo-restricted CTLs against the leukemia-associated protein Wilms tumor antigen Philip Savage, Liquan Gao, Kevin Vento, Pam Cowburn, Stephen Man, Neil Steven, Graham Ogg, Andrew McMichael, Agamemnon Epenetos, Els Goulmy, and Hans J. Stauss From Alexis Biotechnology, London, United Kingdom; Cancer Research Wales, Velindre Hospital, Cardiff, United Kingdom; Department of Immunology, Section of Tumour Immunology, Imperial College, London, United Kingdom; Section of Infection and Immunity, University of Wales College of Medicine, Cardiff, United Kingdom; Division of Cancer Studies, University of Birmingham, Birmingham, United Kingdom; Medical Research Council, Human Immunology Unit, Institute of Molecular Medicine (IMM), Oxford, United Kingdom; Department of Medical Oncology, St Bartholomew's Hospital, London, United Kingdom; and Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, the Netherlands. Recent studies have detected Wilms tumor antigen (WT1)-specific cytotoxic T lymphocytes (CTLs) in patients with acute myelogenous leukemia (AML) and chronic myelogenous leukemia (CML) and demonstrated that most of these CTLs were low avidity. Although HLA-mismatched donors can mount high-avidity CTLs against HLA-A2-presented peptides of WT1, a dominant anti-alloimmune response usually obscures detection of peptide-specific CTLs. Here we explored the feasibility of using recombinant HLA-A2 monomers containing single peptide epitopes as immunogens to generate peptide-specific CTLs from allogeneic donors. We demonstrate that the coating of HLA-A2- B lymphocytes with A2/peptide monomers provides a strong stimulus for autologous peptide-specific CTLs. After 3 to 5 rounds of stimulation a population of CD8+ T cells binding A2/peptide tetramers is easily detectable by fluorescence-activated cell sorting analysis. Furthermore, sorted A2/WT1 tetramer-positive CTLs display strong cytotoxic activity against leukemia cells expressing WT1 endogenously but not against WT1- human tumor cells. Thus, HLA/peptide monomers may be useful to isolate peptide-specific donor lymphocytes for treatment of patients with leukemia after HLA-mismatched transplantation. (Blood. 2004;103:4613-4615) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Generating CTL by HLA transplant Moniek A. de Witte and Ton N. M. Schumacher Blood 2004 103: 4381-4382. [Full Text] [PDF] This article has been cited by other articles: S. Wilde, D. Sommermeyer, B. Frankenberger, M. Schiemann, S. Milosevic, S. Spranger, H. Pohla, W. Uckert, D. H. Busch, and D. J. Schendel Dendritic cells pulsed with RNA encoding allogeneic MHC and antigen induce T cells with superior antitumor activity and higher TCR functional avidity Blood, September 3, 2009; 114(10): 2131 - 2139. [Abstract] [Full Text] [PDF] X. Weng, S. Lu, M. Zhong, Z. Liang, G. Shen, J. Chen, and X. Wu Allo-restricted CTLs generated by coculturing of PBLs and autologous monocytes loaded with allogeneic peptide/HLA/IgG1-Fc fusion protein J. Leukoc. Biol., March 1, 2009; 85(3): 574 - 581. [Abstract] [Full Text] [PDF] C. Chaise, S. L. Buchan, J. Rice, J. Marquet, H. Rouard, M. Kuentz, G. E. Vittes, V. Molinier-Frenkel, J.-P. Farcet, H. J. Stauss, et al. DNA vaccination induces WT1-specific T-cell responses with potential clinical relevance Blood, October 1, 2008; 112(7): 2956 - 2964. [Abstract] [Full Text] [PDF] D. J. Powell Jr., M. E. Dudley, K. A. Hogan, J. R. Wunderlich, and S. A. Rosenberg Adoptive Transfer of Vaccine-Induced Peripheral Blood Mononuclear Cells to Patients with Metastatic Melanoma following Lymphodepletion J. Immunol., November 1, 2006; 177(9): 6527 - 6539. [Abstract] [Full Text] [PDF] M. J. Pittet, A. Gati, F.-A. Le Gal, G. Bioley, P. Guillaume, M. de Smedt, J. Plum, D. E. Speiser, J.-C. Cerottini, P.-Y. Dietrich, et al. Ex Vivo Characterization of Allo-MHC-Restricted T Cells Specific for a Single MHC-Peptide Complex J. Immunol., February 15, 2006; 176(4): 2330 - 2336. [Abstract] [Full Text] [PDF] A. M. E. Whitelegg, L. E. M. Oosten, S. Jordan, M. Kester, A. G. S. van Halteren, J. A. Madrigal, E. Goulmy, and L. D. Barber Investigation of Peptide Involvement in T Cell Allorecognition Using Recombinant HLA Class I Multimers J. Immunol., August 1, 2005; 175(3): 1706 - 1714. [Abstract] [Full Text] [PDF]

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