Submitted April 18, 2008
Accepted August 26, 2008
SWAP-70 regulates RhoA/RhoB-dependent MHCII surface localization in dendritic cells
Carlos Ocana-Morgner, Christine Wahren, and Rolf Jessberger*
Institute of Physiological Chemistry, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden, Germany
* Corresponding author; email: rolf.jessberger{at}tu-dresden.de.
Stimulated dendritic cells (DCs) mature and migrate to lymphoid organs to prime naive T cells. DC maturation augments antigen presentation capacity of DCs by increasing peptide loading, half-life, and cell surface localization of MHC molecules. Activated SWAP-70-/- DCs fail to properly localize MHCII molecules in the plasma membrane, are strongly impaired in T cell activation and altered in F-actin rearrangement. MHCII synthesis, invariant chain removal, and MHCII internalization, however, are unaffected. MHCII surface localization is known to require RhoGTPases. Surprisingly, SWAP70, hitherto known to bind F-actin and Rac, also binds RhoA-GTP. In SWAP-70-/- DCs RhoA and RhoB are stimulus-independent, constitutively active. Surface localization of MHCII molecules and T cell activation can be restored by blocking RhoA and RhoB before but not during DC activation. Thus, contrasting positive regulation of Rac, SWAP-70 negatively regulates RhoA and - indirectly- RhoB, preventing premature RhoA/RhoB activation. Through RhoA/RhoB regulation, SWAP-70 defines a new pathway to control surface localization of MHCII, a critical element in DC dependent immune responses.
