Delivery of Large Heterologous Polypeptides across the Cytoplasmic Membrane of Antigen-Presenting Cells by the Bordetella RTX Hemolysin Moiety Lacking the Adenylyl Cyclase Domain

0378997 - MBÚ 2013 RIV US eng J - Článek v odborném periodiku
Holubová, Jana - Kamanová, Jana - Jelínek, J. - Tomala, Jakub - Mašín, Jiří - Kosová, Martina - Staněk, Ondřej - Bumba, Ladislav - Michálek, J. - Kovář, Marek - Šebo, Peter
Delivery of Large Heterologous Polypeptides across the Cytoplasmic Membrane of Antigen-Presenting Cells by the Bordetella RTX Hemolysin Moiety Lacking the Adenylyl Cyclase Domain.
Infection and Immunity. Roč. 80, č. 3 (2012), s. 1181-1192. ISSN 0019-9567. E-ISSN 1098-5522
Grant CEP: GA AV ČR IAA500200914; GA ČR(CZ) GAP207/11/0717; GA ČR GAP301/11/0325; GA MŠMT 1M0506; GA MŠMT 2B06161
Výzkumný záměr: CEZ:AV0Z50200510
Klíčová slova: MHC CLASS-I * ESCHERICHIA-COLI * PRESENTATION PATHWAY
Kód oboru RIV: EE - Mikrobiologie, virologie
Impakt faktor: 4.074, rok: 2012

The Bordetella adenylate cyclase toxin-hemolysin (CyaA; also called ACT or AC-Hly) targets CD11b-expressing phagocytes and translocates into their cytosol an adenylyl cyclase (AC) that hijacks cellular signaling by conversion of ATP to cyclic AMP (cAMP). Intriguingly, insertion of large passenger peptides removes the enzymatic activity but not the cell-invasive capacity of the AC domain. This has repeatedly been exploited for delivery of heterologous antigens into the cytosolic pathway of CD11b-expressing dendritic cells by CyaA/AC(-) toxoids, thus enabling their processing and presentation on major histocompatibility complex (MHC) class I molecules to cytotoxic CD8(+) T lymphocytes (CTLs). We produced a set of toxoids with overlapping deletions within the first 371 residues of CyaA and showed that the structure of the AC enzyme does not contain any sequences indispensable for its translocation across target cell membrane
Trvalý link: http://hdl.handle.net/11104/0210288