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Infection and Immunity, July 2006, p. 4322-4329, Vol. 74, No. 7
0019-9567/06/$08.00+0     doi:10.1128/IAI.00260-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

The Yersinia enterocolitica Invasin Protein Promotes Major Histocompatibility Complex Class I- and Class II-Restricted T-Cell Responses

O. T. Bühler, C. A. Wiedig, Y. Schmid, G. A. Grassl, E. Bohn, and I. B. Autenrieth*

Institut für Medizinische Mikrobiologie und Hygiene, Universitätsklinikum Tübingen, D-72076 Tübingen, Germany

Received 17 February 2006/ Returned for modification 30 March 2006/ Accepted 20 April 2006

Yersinia enterocolitica invasin (Inv) protein confers internalization into and expression of proinflammatory cytokines by host cells. Both events require binding of Inv to ß1 integrins, which initiates signaling cascades including activation of focal adhesion complexes, Rac1, mitogen-activated protein kinase, and NF-{kappa}B. Here we tested whether Inv might be suitable as a delivery molecule and adjuvant if used as a component of a vaccine. For this purpose, hybrid proteins composed of Inv and ovalbumin (OVA) were prepared, applied as a coating to microparticles, and used for vaccination. Fusion of OVA to Inv did not significantly disturb the ability of Inv to promote host cell binding, internalization, and interleukin-8 (IL-8) secretion when applied as a coating to microparticles. The microparticles were used for vaccination of mice adoptively transferred with OVA-specific T cells from OT-1 or DO11.10 mice. Administration of OVA-Inv-coated microparticles induced OVA-specific T-cell responses. OVA-specific CD4 T cells produced both gamma interferon (IFN-{gamma}) and IL-4 as determined by enzyme-linked immunosorbent assay. Likewise, pronounced OVA-specific CD8 T-cell responses associated with IFN-{gamma} production were observed. Together, these results suggest that Inv might be an attractive tool in vaccination as it confers both host cell uptake and adjuvant activity by engagement of ß1 integrins of host cells, which leads to CD4 as well as CD8 T-cell responses.

* Corresponding author. Mailing address: Institut für Medizinische Mikrobiologie und Hygiene, Universitätsklinikum Tübingen, Elfriede-Aulhorn-Str. 6, D-72060 Tübingen, Germany. Phone: 49-7071-29 82351. Fax: 49-7071-29 5440. E-mail: Ingo.Autenrieth{at}med.uni-tuebingen.de.

Editor: J. B. Bliska

Infection and Immunity, July 2006, p. 4322-4329, Vol. 74, No. 7
0019-9567/06/$08.00+0     doi:10.1128/IAI.00260-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.





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