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

2009; Oxford University Press; Volume: 86; Issue: 1 Linguagem: Inglês

10.1189/jlb.0608344

1938-3673

Annegret Reinhold, Sibylle Reimann, Dirk Reinhold, Burkhart Schraven, Mauro Togni,

Immune Cell Function and Interaction

Abstract The genetic deletion of SKAP-HOM, an ubiquitously expressed cytosolic adapter protein, affected DC:T cell interactions reducing immune response. 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.