T 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.

2.50
Hdl Handle:
http://hdl.handle.net/10541/71915
Title:
T 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.
Authors:
Hombach, Andreas A; Schildgen, Verena; Heuser, Claudia; Finnern, Ricarda; Gilham, David E; Abken, Hinrich
Abstract:
Recombinant 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.
Affiliation:
Klinik I für Innere Medizin, Tumorgenetik, Kliniken der Universität zu Köln and Zentrum für Molekulare Medizin Köln, Josef-Stelzmann Strasse 9, Köln, Germany.
Citation:
T 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.
Journal:
Journal of Immunology
Issue Date:
1-Apr-2007
URI:
http://hdl.handle.net/10541/71915
PubMed ID:
17372024
Type:
Article
Language:
en
ISSN:
0022-1767
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
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.en
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
All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.