Staphylococcus aureus enterotoxin C2 mutants: biological activity assay in vitro.
Staphylococcal enterotoxin C2 (SEC2) is one member of bacterial superantigens produced by Staphylococcus aureus. It can be attributed to its superantigenic activity to cross-link major histocompatibility complex class II molecules with T-cell receptors and activate a large number of resting T cells resulting in release of massive cytokines, which will produce significant tumor inhibition in vivo and in vitro. However, it could be not broadly applied to cure malignant tumors in clinic because of emetic activity of SEC2. The aim of this study was to inactivate emetic activity of SEC2 through site-directed mutagenesis. Cys93, Cys110 and His118 were selected as substitutional sites based on the functional sites responsible for emesis. The mutated proteins were used to determine Peripheral blood mononuclear cell proliferation activity and anti-tumor activity in vitro. Results showed that these mutated proteins efficiently stimulated T cell and exhibited the same tumor-inhibition effect as SEC2. It is possible to inactivate emetic activity of SEC2 through site-directed mutagenesis and provide satisfying agents for tumor treatment in clinic.
Hui
Jing
J
School of Life Science, Liaoning University, Shenyang, 110036, China.
Cao
Yan
Y
Xiao
Fang
F
Zhang
Jin
J
Li
Hui
H
Hu
Fengqing
F
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001681:Biological Assay; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004639:Emetics / Q000494:pharmacology; D004768:Enterotoxins / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D005289:Ferrets; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D016297:Mutagenesis, Site-Directed; D013211:Staphylococcus aureus / Q000235:genetics*; D014357:Trypsin / Q000378:metabolism
D000970:Antineoplastic Agents; D004639:Emetics; D004768:Enterotoxins; C034959:enterotoxin C, staphylococcal; D014357:Trypsin