Enhanced maturation and functional capacity of dendritic cells induced by mannosylated L2 domain of ErbB2 receptor.
The nature of antigens and functional state of dendritic cells (DC) are important in antigen presentation. The ability of DC for the induction of T-cell responses is promoted by maturation. It has been confirmed that mannose receptors mediate highly efficient endocytosis and presentation of mannosylated proteins. In the present study, L2 domain of ErbB2 ectodomain was expressed in Escherichia coli, purified and mannosylated. The maturation and functional capacity of DC induced by mannosylated L2 (mL2) protein were investigated. The results showed that L2 protein could induce DC maturation, which was accompanied by elevated expression of MHC and co-stimulatory molecules. The effect of mL2 protein on DC maturation was more remarkable than that of non-mL2 proteins. Uptake of mL2 antigens by DC was more efficient. Furthermore, the T cells can be stimulated to proliferate in vitro and secrete Th1 and Th2 cytokines. Higher levels of both IFN-gamma and IL-10 were detected from the T cells stimulated by mL2-pulsed DC, suggesting a concurrent activation of CD4+ and CD8+ T cells. The results demonstrated that L2 domain of ErbB2 receptor is an immunodominant molecule. The mL2 domain of ErbB2 can induce an enhanced maturation and functional capacity of DC. It may become an effective strategy to induce anti-ErbB2 response.
Zhong
G
G
Institute of Basic Medical Sciences, Beijing, China.
Wang
J
J
Xu
M
M
Xie
Z
Z
Yu
M
M
Wang
J
J
Zhou
T
T
Gong
W
W
Sun
Y
Y
Hu
M
M
Zhang
X
X
Shen
B
B
Guo
N
N
D017951:Antigen Presentation / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D018734:Genes, erbB-2 / Q000276:immunology; D006649:Histocompatibility Antigens / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008358:Mannose / Q000276:immunology* / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D006649:Histocompatibility Antigens; D007371:Interferon-gamma; D016753:Interleukin-10; D008358:Mannose; D018719:Erb-b2 Receptor Tyrosine Kinases; D011994:Recombinant Proteins