Chimera of IL-2 Linked to Light Chain of anti-IL-2 mAb Mimics IL-2/anti-IL-2 mAb Complexes Both Structurally and Functionally

0399622 - MBÚ 2014 RIV US eng J - Článek v odborném periodiku
Tomala, Jakub - Kovářová, Jiřina - Kabešová, Martina - Votavová, Petra - Chmelová, Helena - Dvořáková, Barbora - Říhová, Blanka - Kovář, Marek
Chimera of IL-2 Linked to Light Chain of anti-IL-2 mAb Mimics IL-2/anti-IL-2 mAb Complexes Both Structurally and Functionally.
ACS Chemical Biology. Roč. 8, č. 5 (2013), s. 871-876. ISSN 1554-8929. E-ISSN 1554-8937
Grant CEP: GA ČR GAP301/11/0325
Institucionální podpora: RVO:61388971
Klíčová slova: IN-VIVO EXPANSION * IL-2 * ANTIBODY
Kód oboru RIV: CE - Biochemie
Impakt faktor: 5.356, rok: 2013

IL-2/anti-IL-2 mAb immunocomplexes were described to have dramatically higher activity than free IL-2 in vivo. We designed protein chimera consisting of IL-2 linked to light chain of anti-IL-2 mAb S4B6 through flexible oligopeptide spacer (Gly(4)Ser)(3). This protein chimera mimics the structure of IL-2/S4B6 mAb immunocomplexes but eliminates general disadvantages of immunocomplexes like possible excess of either IL-2 or anti-IL-2 mAb and their dissociation to antibody and IL-2 at low concentrations. This novel kind of protein chimera is characterized by an intramolecular interaction between IL-2 and binding site of S4B6 mAb similarly as in IL-2/S4B6 mAb immunocomplexes. Our protein chimera has biological activity comparable to IL-2/S4B6 mAb immunocomplexes in vitro, as shown by stimulation of proliferation of purified and activated OT-I CD8(+) T cells. The protein chimera exerts higher stimulatory activity to drive expansion of purified CFSE-labeled OT-I CD8(+) T cells activated by an injection of a low dose of SIINFEKL peptide than IL-2/S4B6 mAb immunocomplexes in vivo
Trvalý link: http://hdl.handle.net/11104/0227039