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Blood, 15 September 2007, Vol. 110, No. 6, pp. 1997-2004. Prepublished online as a Blood First Edition Paper on June 5, 2007; DOI 10.1182/blood-2006-12-064444. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-12-064444v1 110/6/1997    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 Sashchenko, L. P Articles by Georgiev, G. P Search for Related Content PubMed PubMed Citation Articles by Sashchenko, L. P Articles by Georgiev, G. P Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 26, 2006 Accepted May 29, 2007 Cytotoxic T lymphocytes carrying a pattern recognition protein Tag7 can detect evasive, HLA-negative but Hsp70-exposing tumor cells, thereby ensuring FasL/Fas-mediated contact killing Lidia P Sashchenko*, Elena A Dukhanina, Yury V Shatalov, Denis V Yashin, Tamara I Lukyanova, Olga D Kabanova, Elena A Romanova, Sergei V Khaidukov, Alexander V Galkin, Nikolai V Gnuchev, and Georgii P Georgiev Laboratory of Immunogenetics of Cancer, Institute of Gene Biology, Russian Academy of Sciences (RAS), Moscow, Russian Federation Laboratory Biosyntesis of nucleic acids, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences RAS, Moscow, Russian Federation University of Oslo, Centre for Medical Studies in Russia, Moscow, Russian Federation Laboratory of Instrumental Methods of Analysis, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, RAS, Moscow, Russian Federation * Corresponding author; email: sashchenko{at}genebiology.ru. Within the broad problem of host immune surveillance versus tumor immune evasion, a most intriguing question is how the cellular immunity can cope with cancerous cells that have got rid of the classical antigen-presenting machinery. One such option stems from (i) the fact that HLA loss is often attended with expression of Hsp70 on the tumor cell surface, and (ii) our findings that human lymphocytes express a protein Tag7 (aka PGRP-S) capable of tight and specific interaction with cognate Hsp70. Here we show that a subpopulation of human CD4+CD25+ lymphocytes, obtained either in culture as lymphokine-activated killers or directly from healthy donors, carry Tag7 and FasL on their surface and can indeed kill HLA-negative tumor-derived cells K562 and MOLT-4 that expose Hsp70 and Fas. The primary binding of lymphocyte Tag7 to target-cell Hsp70 is very specific (e.g., it is blocked by preincubating either cell with minimal peptides from the "partner" protein) and secures cell contact indispensable for subsequent FasL/Fas-triggered apoptosis. Unrelated to NK action or the putative role of Hsp as an antigen-presenting substitute, this novel mechanism is rather a backup analog of orthodox (CD8+) target recognition (Tag7 acting as built-in TCR and Hsp70 itself as ligand). CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. A. Dukhanina, O. D. Kabanova, T. I. Lukyanova, Y. V. Shatalov, D. V. Yashin, E. A. Romanova, N. V. Gnuchev, A. V. Galkin, G. P. Georgiev, and L. P. Sashchenko Opposite roles of metastasin (S100A4) in two potentially tumoricidal mechanisms involving human lymphocyte protein Tag7 and Hsp70 PNAS, August 18, 2009; 106(33): 13963 - 13967. [Abstract] [Full Text] [PDF]

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