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dc.contributor.authorHombach, Andreas A
dc.contributor.authorSchildgen, Verena
dc.contributor.authorHeuser, Claudia
dc.contributor.authorFinnern, Ricarda
dc.contributor.authorGilham, David E
dc.contributor.authorAbken, Hinrich
dc.date.accessioned2009-06-30T10:43:41Z
dc.date.available2009-06-30T10:43:41Z
dc.date.issued2007-04-01
dc.identifier.citationT cell activation by antibody-like immunoreceptors: the position of the binding epitope within the target molecule determines the efficiency of activation of redirected T cells. 2007, 178 (7):4650-7 J. Immunol.en
dc.identifier.issn0022-1767
dc.identifier.pmid17372024
dc.identifier.urihttp://hdl.handle.net/10541/71915
dc.description.abstractRecombinant TCRs confer specificity to T cells and trigger their activation. Receptors with Ab-derived binding domains have the advantages of MHC-independent Ag recognition and of targeting a variety of chemically different molecules. We explored the impact of the position of a defined epitope within the target molecule on the efficacy of receptor-mediated T cell activation. T cells were grafted with recombinant immunoreceptors that recognize either the membrane distal N or the proximal A3 domain of carcinoembryonic Ag (CEA). Upon binding to isolated, solid-phase immobilized CEA, receptor-mediated T cell activation correlates with the binding efficiency, irrespectively, of the epitope position. Upon binding to CEA expressed on the cell membrane, in contrast, the A3 epitope mediates more efficiently T cell activation than the N epitope, although the N epitope is bound with higher affinity. The CEA N epitope when expressed in a more membrane proximal position, however, activated receptor grafted T cells with higher efficiency than in the distal position. The position of the targeted epitope within the molecule obviously has major impact on the efficacy of T cell activation independently of the binding efficiency of the immunoreceptor.
dc.language.isoenen
dc.subject.meshAntibodies
dc.subject.meshCarcinoembryonic Antigen
dc.subject.meshEpitopes
dc.subject.meshHumans
dc.subject.meshLymphocyte Activation
dc.subject.meshProtein Structure, Tertiary
dc.subject.meshReceptors, Immunologic
dc.subject.meshRecombinant Proteins
dc.subject.meshT-Lymphocytes
dc.titleT cell activation by antibody-like immunoreceptors: the position of the binding epitope within the target molecule determines the efficiency of activation of redirected T cells.en
dc.typeArticleen
dc.contributor.departmentKlinik I für Innere Medizin, Tumorgenetik, Kliniken der Universität zu Köln and Zentrum für Molekulare Medizin Köln, Josef-Stelzmann Strasse 9, Köln, Germany.en
dc.identifier.journalJournal of Immunologyen
html.description.abstractRecombinant TCRs confer specificity to T cells and trigger their activation. Receptors with Ab-derived binding domains have the advantages of MHC-independent Ag recognition and of targeting a variety of chemically different molecules. We explored the impact of the position of a defined epitope within the target molecule on the efficacy of receptor-mediated T cell activation. T cells were grafted with recombinant immunoreceptors that recognize either the membrane distal N or the proximal A3 domain of carcinoembryonic Ag (CEA). Upon binding to isolated, solid-phase immobilized CEA, receptor-mediated T cell activation correlates with the binding efficiency, irrespectively, of the epitope position. Upon binding to CEA expressed on the cell membrane, in contrast, the A3 epitope mediates more efficiently T cell activation than the N epitope, although the N epitope is bound with higher affinity. The CEA N epitope when expressed in a more membrane proximal position, however, activated receptor grafted T cells with higher efficiency than in the distal position. The position of the targeted epitope within the molecule obviously has major impact on the efficacy of T cell activation independently of the binding efficiency of the immunoreceptor.


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