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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 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 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 Trivedi, D. Articles by Koehne, G. Search for Related Content PubMed PubMed Citation Articles by Trivedi, D. Articles by Koehne, G. Related Collections Immunobiology Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Generation of CMV-specific T lymphocytes using protein-spanning pools of pp65-derived overlapping pentadecapeptides for adoptive immunotherapy Deepa Trivedi, Roxanne Y. Williams, Richard J. O'Reilly, and Guenther Koehne From the Allogeneic Bone Marrow Transplantation Service, Department of Pediatrics, Transplantation Biology Laboratory, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY. Cell-mediated immunity is essential for control of human cytomegalovirus (HCMV) infection. We used a pool of 138 synthetic overlapping pentadecapeptides overspanning 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 that 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 HLAalleles. HLA-A*0201+ donors consistently responded to pentadecapeptides containing HLA-A*0201-binding epitopeaa495-503NLVPMVATV. 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 aa341-350QYDPVAALF (HLA-A*2402) as well as unreported epitopes such as aa267-275HERNGFTVL (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 that 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: 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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