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Nauerth, M.* ; Weißbrich, B.* ; Knall, R.* ; Franz, T.* ; Dössinger, G.* ; Bet, J.* ; Paszkiewicz, P.J.* ; Pfeifer, L.* ; Bunse, M.* ; Uckert, W.* ; Holtappels, R.* ; Gillert-Marien, D.* ; Neuenhahn, M. ; Krackhardt, A.M. ; Reddehase, M.J.* ; Riddell, S.R.* ; Busch, D.H.

TCR-Ligand koff rate correlates with the protective capacity of antigen-specific CD8+ T cells for adoptive transfer.

Sci. Transl. Med. 5:192ra87 (2013)
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Adoptive immunotherapy is a promising therapeutic approach for the treatment of chronic infections and cancer. T cells within a certain range of high avidity for their cognate ligand are believed to be most effective. T cell receptor (TCR) transfer experiments indicate that a major part of avidity is hardwired within the structure of the TCR. Unfortunately, rapid measurement of structural avidity of TCRs is difficult on living T cells. We developed a technology where dissociation (k(off) rate) of truly monomeric peptide-major histocompatibility complex (pMHC) molecules bound to surface-expressed TCRs can be monitored by real-time microscopy in a highly reliable manner. A first evaluation of this method on distinct human cytomegalovirus (CMV)-specific T cell populations revealed unexpected differences in the k(off) rates. CMV-specific T cells are currently being evaluated in clinical trials for efficacy in adoptive immunotherapy; therefore, determination of koff rates could guide selection of the most effective donor cells. Indeed, in two different murine infection models, we demonstrate that T cell populations with lower k(off) rates confer significantly better protection than populations with fast k(off) rates. These data indicate that k(off) rate measurements can improve the predictability of adoptive immunotherapy and provide diagnostic information on the in vivo quality of T cells.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Superior Antitumor-activity ; Gene-transfer ; High-avidity ; Selective Expansion ; Reactive Tcr ; Lymphocytes ; Cytomegalovirus ; Mhc ; Reconstitution ; Infection
Sprache englisch
Veröffentlichungsjahr 2013
HGF-Berichtsjahr 2013
ISSN (print) / ISBN 1946-6234
e-ISSN 1946-6242
Zeitschrift Science Translational Medicine
Quellenangaben Band: 5, Heft: 192, Seiten: , Artikelnummer: 192ra87 Supplement: ,
Verlag American Association for the Advancement of Science (AAAS)
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)
Institute of Molecular Immunology (IMI)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-520100-001
G-501790-003
PubMed ID 23825303
DOI 10.1126/scitranslmed.3005958
WOS ID WOS:000321257600008
Erfassungsdatum 2013-08-02
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