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Originally published online as doi:10.1189/jlb.0608344 on April 15, 2009

Published online before print April 15, 2009
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(Journal of Leukocyte Biology. 2009;86:61-71.)
© 2009 Society for Leukocyte Biology

Expression of SKAP-HOM in DCs is required for an optimal immune response in vivo

Annegret Reinhold, Sibylle Reimann, Dirk Reinhold, Burkhart Schraven and Mauro Togni1

Institute of Molecular and Clinical Immunology, Otto von Guericke University, Magdeburg, Germany

1. Correspondence: Institute of Molecular and Clinical Immunology, Otto von Guericke University, Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany. E-mail: mauro.togni{at}med.ovgu.de

ABSTRACT

The cytosolic adaptor molecule SKAP-HOM, similar to the T cell-specific homologue SKAP55, interacts directly with ADAP, and both molecules are involved in inside-out signaling. Previous studies have shown that in the absence of SKAP-HOM, antigen receptor-triggered integrin-mediated adhesion is impaired severely in B cells but not in T cells. In addition, loss of SKAP-HOM results in a less severe clinical course of EAE. DCs are the most potent APCs and express SKAP-HOM. However, the role of SKAP-HOM in DCs remains unknown. Here, we assessed whether the reduced severity of EAE observed in SKAP-HOM-deficient mice is at least partially a result of an impaired cooperation between APCs and T cells. We demonstrate that migration of LC in vivo and the spontaneous motility of BMDCs in vitro are increased in the absence of SKAP-HOM. In contrast, triggering of the integrin results in a drastic decrease of DC motility and in enhanced actin polymerization in SKAP-HOM-deficient DCs. Furthermore, the antigen-dependent conjugate formed between wild-type T cells and SKAP-HOM–/– DCs is delayed in comparison with wild-type DCs. Strikingly, fewer antigen-specific T cells are induced by immunization with SKAP-HOM–/– BMDCs as compared with wild-type BMDCs in vivo. Thus, these findings suggest that SKAP-HOM expression in DCs is required for the induction of an optimal immune response.

Key Words: adaptor molecules • antigen presentation • EAE




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