Abstract Antigen presenting cells (APC) initiate immune responses against pathogens by presenting antigen and costimulatory signals to T lymphocytes. APCs loaded with antigens in vitro have been used as therapeutic vaccines to induce antiviral or tumour immune responses in chronic infectious diseases or cancer. However, the live APCs are unstable in vivo and cannot overcome the immune tolerance induced by persistent viral infection or tumour microenvironment. We have developed nano-sized APCs that are at the size of ~ 500nM and can present antigen, costimulatory molecules and bioengineered IL-2 to antigen specific T cells directly. The nano-APCs are prepared from isolated endoplasmic reticulum membranes of APCs engineered with an ER-retained IL-2. Assembled with specific antigenic peptides, the nano-APC effectively induce responses of CMV or HBV specific CD4 and/or CD8 T cells responses in peripheral blood lymphocytes (PBL) of CMV serum converted or chronic HBV infected patients. With selected antigens, the bio-engineered nano-APCs will be used as therapeutic vaccines for the treatment of chronic HBV, HCV or HIV infection and also cancer.

To understand the function of the suppressor of cytokine signaling (SOCS)-7, we have looked for proteins interacting with SOCS-7 in a stringent yeast two-hybrid screen of a human leukocyte cDNA-library. We identified the cytoskeletal molecule vinexin as a partner interacting with SOCS-7. Tests with deletion mutants of SOCS-7 demonstrated that a central region of the molecule containing several proline-rich regions, N-terminal to the SH2 domain, was responsible for the binding to vinexin. It is thus likely that one of the SH3 domains of vinexin interacts with a poly-proline region of SOCS-7. The interaction with vinexin was confirmed biochemically as vinexin-alpha was co-precipitated with SOCS-7. Confocal laser-scanning microscopy in HEK293T, MCF-7, and 3T3-L1 cells showed that part of the transfected SOCS-7-green fluorescent protein (GFP) molecules merged with vinexin and with actin. Taken together, our data indicate that SOCS-7 interacts with vinexin and the actin cytoskeleton.