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 | Größe | Format | |
---|---|---|---|---|
Bewarder2020_Article_CharacterizationOfAnHLA-restri.pdf | 1,48 MB | Adobe PDF | Öffnen/Anzeigen |
Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons