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Blood, 1 April 2005, Vol. 105, No. 7, pp. 2793-2801. Prepublished online as a Blood First Edition Paper on October 28, 2004; DOI 10.1182/blood-2003-05-1433. This Article Full Text (PDF) All Versions of this Article: 2003-05-1433v1 105/7/2793    most recent Alert me when this article is cited Alert me if a correction is posted 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 Trivedi, D. Articles by Koehne, G. Search for Related Content PubMed PubMed Citation Articles by Trivedi, D. Articles by Koehne, G. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 7, 2003 Accepted October 25, 2004 Generation of Cytomegalovirus (CMV)-specific T lymphocytes using protein-spanning pools of pp65-derived pentadecapeptides for adoptive immunotherapy Deepa Trivedi, Roxanne Y Williams, Richard J O'Reilly, and Guenther Koehne* Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; Transplantation Biology Laboratory, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY, USA Transplantation Biology Laboratory, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY, USA Allogeneic Bone Marrow Transplantation Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; Transplantation Biology Laboratory, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY, USA Allogeneic Bone Marrow Transplantation Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; Transplantation Biology Laboratory, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY, USA * Corresponding author; email: guenther_koehne{at}rush.edu. Cell-mediated immunity is essential for control of human cytomegalovirus (HCMV) infection. We utilized a pool of 138 synthetic overlapping pentadecapeptides over-spanning the entire pp65 protein to generate polyclonal CMV-specific T-cell lines from 12 CMV-seropositive donors inheriting different HLA genotypes. Autologous monocyte-derived dendritic cells (DCs) pulsed with this complete pool consistently induced highly specific T-cells which selectively recognized 1-3 pentadecapeptides identified by secondary responses to a mapping grid of pentadecapeptide subpools with single overlaps. Responses against peptide loaded targets sharing single HLA class I or II alleles identified the restricting HLA alleles. HLA-A*0201+ donors consistently responded to pentadecapeptides containing HLA-A*0201 binding epitope aa 495-503 NLVPMVATV. T-cell lines from other donors contained high frequencies of CD4 and/or CD8 T-cells selectively reactive against peptides presented by other HLA alleles including both known epitopes such as aa 341-350QYDPVAALF (HLA-A*2402) as well as unreported epitopes such as aa 267-275HERNGFTVL (HLA-B*4001 and B* 4002) and aa513-523FFWDANDIYRI (HLA-DRB1* 1301). These T-cells consistently lysed CMV-infected target cells. Thus, this approach fosters expansion and selection of HLA-restricted CMV-pp65-reactive T-cell lines of high specificity which also lyse CMV-infected targets, and from a functional and regulatory perspective, may have advantages for generating virus-specific T-cells for adoptive immunotherapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. N. Hasan, W. J. Kollen, D. Trivedi, A. Selvakumar, B. Dupont, M. Sadelain, and R. J. O'Reilly A Panel of Artificial APCs Expressing Prevalent HLA Alleles Permits Generation of Cytotoxic T Cells Specific for Both Dominant and Subdominant Viral Epitopes for Adoptive Therapy J. Immunol., August 15, 2009; 183(4): 2837 - 2850. [Abstract] [Full Text] [PDF] D. M. Andrews, C. E. Andoniou, P. Fleming, M. J. Smyth, and M. A. Degli-Esposti The Early Kinetics of Cytomegalovirus-Specific CD8+ T-Cell Responses Are Not Affected by Antigen Load or the Absence of Perforin or Gamma Interferon J. Virol., May 15, 2008; 82(10): 4931 - 4937. [Abstract] [Full Text] [PDF] S. W. Howland and K. D. Wittrup Antigen Release Kinetics in the Phagosome Are Critical to Cross-Presentation Efficiency J. Immunol., February 1, 2008; 180(3): 1576 - 1583. [Abstract] [Full Text] [PDF] M. Wolfl, J. Kuball, W. Y. Ho, H. Nguyen, T. J. Manley, M. Bleakley, and P. D. Greenberg Activation-induced expression of CD137 permits detection, isolation, and expansion of the full repertoire of CD8+ T cells responding to antigen without requiring knowledge of epitope specificities Blood, July 1, 2007; 110(1): 201 - 210. [Abstract] [Full Text] [PDF] K.-D. Park, L. Marti, J. Kurtzberg, and P. Szabolcs In vitro priming and expansion of cytomegalovirus-specific Th1 and Tc1 T cells from naive cord blood lymphocytes Blood, September 1, 2006; 108(5): 1770 - 1773. [Abstract] [Full Text] [PDF]

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