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Blood, 15 April 2007, Vol. 109, No. 8, pp. 3300-3307. Prepublished online as a Blood First Edition Paper on December 19, 2006; DOI 10.1182/blood-2006-06-028001. This Article Full Text (PDF) All Versions of this Article: blood-2006-06-028001v1 109/8/3300    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 Hess, P. R. Articles by Frelinger, J. A. Search for Related Content PubMed PubMed Citation Articles by Hess, P. R. Articles by Frelinger, J. A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 8, 2006 Accepted December 12, 2006 Selective deletion of antigen-specific CD8+ T cells by MHC class I tetramers coupled to the type I ribosome-inactivating protein, saporin Paul R. Hess*, Carie Barnes, Matthew D. Woolard, Michael D. L. Johnson, John M. Cullen, Edward J. Collins, and Jeffrey A. Frelinger Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, United States Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States * Corresponding author; email: paul_hess{at}ncsu.edu. CD8+ cytotoxic T lymphocytes (CTL) are important effector cells responsible for tissue destruction in several autoimmune and allograft-related diseases. To discover if pathogenic T cells could be selectively deleted, we investigated the ability of a toxin coupled to major histocompatibility complex (MHC) class I tetramers to kill antigen-specific CD8+ T cells. H2-Db tetramers were assembled using streptavidin conjugated to the ribosome-inactivating protein (RIP), saporin (SAP). These tetramers inhibited ribosome activity in vitro, retained the T cell receptor (TCR) binding specificity of their non-toxic counterparts, and were internalized by 100% of target cells, leading to cell death in 72 hours. Cytotoxicity was dependent on the tetramer dose and avidity for the T cell. A single injection of the SAP-coupled tetramer eliminated >75% of cognate, but not control, T cells. This work demonstrates the therapeutic potential of cytotoxic tetramers to selectively eradicate pathogenic clonotypes, while leaving overall T cell immunity intact. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Schutz, M. Fleck, A. Mackensen, A. Zoso, D. Halbritter, J. P. Schneck, and M. Oelke Killer artificial antigen-presenting cells: a novel strategy to delete specific T cells Blood, April 1, 2008; 111(7): 3546 - 3552. [Abstract] [Full Text] [PDF] A. N.-S. Mak, Y.-T. Wong, Y.-J. An, S.-S. Cha, K.-H. Sze, S. W.-N. Au, K.-B. Wong, and P.-C. Shaw Structure-function study of maize ribosome-inactivating protein: implications for the internal inactivation region and the sole glutamate in the active site Nucleic Acids Res., September 25, 2007; 35(18): 6259 - 6267. [Abstract] [Full Text] [PDF]

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