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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0608344

Received for publication June 9, 2008.
Revised February 19, 2009.
Accepted for publication February 25, 2009.

Article

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 Togni @

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

@ To whom correspondence should be addressed. E-mail: mauro.togni{at}med.ovgu.de.


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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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