Bitte benutzen Sie diese Referenz, um auf diese Ressource zu verweisen: doi:10.22028/D291-33821
Titel: Characterization of an HLA-restricted and human cytomegalovirus-specific antibody repertoire with therapeutic potential
VerfasserIn: Bewarder, Moritz
Held, Gerhard
Thurner, Lorenz
Stilgenbauer, Stephan
Smola, Sigrun
Preuss, Klaus-Dieter
Carbon, Gabi
Bette, Birgit
Christofyllakis, Konstantinos
Bittenbring, Joerg Thomas
Felbel, Arne
Hasse, Alexander
Murawski, Niels
Kaddu-Mulindwa, Dominic
Neumann, Frank
Sprache: Englisch
Titel: Cancer Immunology, Immunotherapy
Bandnummer: 69
Heft: 8
Seiten: 1535–1548
Verlag/Plattform: Springer Nature
Erscheinungsjahr: 2020
Freie Schlagwörter: HCMV infection
Immunosuppression
Allogeneic stem cell transplantation
TCR-like antibodies
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: With an infection rate of 60–90%, the human cytomegalovirus (HCMV) is very common among adults but normally causes no symptoms. When T cell-mediated immunity is compromised, HCMV reactivation can lead to increased morbidity and mortality. HCMV antigens are processed and presented as peptides on the cell surface via HLA I complexes to the T cell receptor (TCR) of T cells. The generation of antibodies against HCMV peptides presented on HLA complexes (TCR-like antibodies) has been described, but is without therapeutic applications to date due to the polygenic and polymorphic nature of HLA genes. We set out to obtain antibodies specific for HLA/HCMV-peptides, covering the majority of HLA alleles present in European populations. Using phage display technology, we selected 10 Fabs, able to bind to HCMV-peptides presented in the 6 different HLA class I alleles A*0101, A*0201, A*2402, B*0702, B*0801 and B*3501. We demonstrate specific binding of all selected Fabs to HLA-typed lymphoblastoid cell lines (EBV-transformed B cells) and lymphocytes loaded with HCMV-peptides. After infection with HCMV, 4/10 tetramerized Fabs restricted to the alleles HLA-A*0101, HLA-A*0201 and HLA-B*0702 showed binding to infected primary fibroblasts. When linked to the pseudomonas exotoxin A, these Fab antibodies induce highly specific cytotoxicity in HLA matched cell lines loaded with HCMV peptides. TCR-like antibody repertoires therefore represent a promising new treatment modality for viral infections and may also have applications in the treatment of cancers.
DOI der Erstveröffentlichung: 10.1007/s00262-020-02564-1
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-338217
hdl:20.500.11880/31143
http://dx.doi.org/10.22028/D291-33821
ISSN: 1432-0851
0340-7004
Datum des Eintrags: 13-Apr-2021
Bezeichnung des in Beziehung stehenden Objekts: Electronic supplementary material
In Beziehung stehendes Objekt: https://static-content.springer.com/esm/art%3A10.1007%2Fs00262-020-02564-1/MediaObjects/262_2020_2564_MOESM1_ESM.pdf
Fakultät: M - Medizinische Fakultät
Fachrichtung: M - Innere Medizin
Professur: M - Prof. Dr. Stephan Stilgenbauer
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

Dateien zu diesem Datensatz:
Datei Beschreibung GrößeFormat 
Bewarder2020_Article_CharacterizationOfAnHLA-restri.pdf1,48 MBAdobe PDFÖffnen/Anzeigen


Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons Creative Commons