The extra domain A from fibronectin targets antigens to TLR4-expressing cells and induces cytotoxic T cell responses in vivo
Lasarte JJ, Casares N, Gorraiz M, Hervás-Stubbs S, Arribillaga L, Mansilla C, Durantez M, Llopiz D, Sarobe P, Borrás-Cuesta F, Prieto J, Leclerc C.
Area de Hepatología y Terapia Génica, Universidad de Navarra, Centro de Investigación Médica Aplicada, Avenida Pío XII 55, 31008 Pamplona, Spain
Magazine: Journal of Immunology
Date: Jan 15, 2007Hepatology
Vaccination strategies based on the in vivo targeting of Ags to dendritic cells (DCs) are needed to improve the induction of specific T cell immunity against tumors and infectious agents. In this study, we have used a recombinant protein encompassing the extra domain A from fibronectin (EDA), an endogenous ligand for TLR4, to deliver Ags to TLR4-expressing DC.
The purified EDA protein was shown to bind to TLR4-expressing HEK293 cells and to activate the TLR4 signaling pathway. EDA also stimulated the production by DC of proinflammatory cytokines such as IL-12 or TNF-alpha and induced their maturation in vitro and in vivo.
A fusion protein between EDA and a cytotoxic T cell epitope from OVA efficiently presented this epitope to specific T cells and induced the in vivo activation of a strong and specific CTL response. Moreover, a fusion protein containing EDA and the full OVA also improved OVA presentation by DC and induced CTL responses in vivo. These EDA recombinant proteins protected mice from a challenge with tumor cells expressing OVA.
These results strongly suggest that the fibronectin extra domain A may serve as a suitable Ag carrier for the development of antiviral or antitumoral vaccines.
CITATION J Immunol. 2007 Jan 15;178(2):748-56
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