Tripeptide of FcyRIIA

Abstract

The present invention relates, in general, to phagocytosis and phagolysosomal fusion and, in particular, to a tripeptide of FcγRIIA that mediates trafficking of targets phagocytosed via FcγRIIA to the lysosomal compartment.

1 . A method of mediating trafficking of a target to a lysosomal compartment of a cell comprising associating with said target a molecule containing an L-T-L peptide under conditions such that said trafficking is effected, wherein said molecule is other than an FcγRIIA molecule endogenous to said cell.  
     
     
         2 . The method according to  claim 1  wherein said target is a bacterium.  
     
     
         3 . A method of enhancing the ability of a cell to degrade a particle comprising introducing into said cell a nucleic acid sequence encoding an Fc receptor comprising an L-T-L sequence under conditions such that said nucleic acid sequence is expressed and said enhancement is effected.  
     
     
         4 . The method according to  claim 3  wherein said Fc receptor is FcγRIIA or a modified form thereof comprising at least 1 additional L-T-L peptide in the cytoplasmic domain thereof.  
     
     
         5 . The method according to  claim 3  wherein said Fc receptor comprises a γ chain comprising at least one L-T-L peptide in the cytoplasmic domain thereof.  
     
     
         6 . The method according to  claim 3  wherein said cell naturally expresses FcγRIIA.  
     
     
         7 . The method according to  claim 3  wherein said cell does not naturally express FcγRIIA.  
     
     
         8 . The method according to  claim 3  wherein said cell is an endothelial cell, a fibroblast, a macrophage or an epithelial cell.  
     
     
         9 . The method according to  claim 3  wherein said particle is a bacterium.  
     
     
         10 . The method according to  claim 3  wherein said nucleic acid sequence is introduced into said cell in a liposome, a bacterium or a viral vector.  
     
     
         11 . A method of enhancing the ability of a cell that has on its surface FcγRIIA to degrade a particle comprising contacting said cell with an agent that increases the number of FcγRIIA molecules present on the surface of said cell so that said enhancement is effected.  
     
     
         12 . The method according to  claim 11  wherein said cell is a macrophage.  
     
     
         13 . The method according to  claim 11  wherein said agent is IFN-γ or an inhibitor of IL-4.  
     
     
         14 . A method of targeting a particle to an FcγRIIA molecule present on a cell comprising contacting said particle with a bi-specific antibody that recognizes said particle and the extracellular domain of said FcγRIIA under conditions such that said antibody binds said particle and said FcγRIIA so that said targeting is effected.  
     
     
         15 . The method according to  claim 14  wherein said particle is a microorganism.  
     
     
         16 . A method of inducing uptake and targeting of a particle to a phagolysosome of a cell comprising contacting said particle with an IgG antibody that recognizes said particle, which antibody has associated therewith an L-T-L-containing peptide, wherein said contacting is effected under conditions such that said antibody binds said particle and said induction is effected.  
     
     
         17 . The method according to  claim 16  wherein said particle is an immune complex.  
     
     
         18 . The method according to  claim 16  wherein said particle is a microorganism.  
     
     
         19 . A method of inducing targeting of a particle to a phagolysosome of a cell comprising contacting said particle with an L-T-L-containing peptide, wherein said contacting is effected under conditions such that said an L-T-L-containing peptide associates with said particle and said induction is thereby effected.  
     
     
         20 . A method of inhibiting degradation of a particle by a phagolysosome of a cell comprising contacting said cell with an agent that inhibits the function of L-T-L-containing molecule present in said cell so that said inhibition is effected.  
     
     
         21 . The method according to  claim 2  wherein said bacterium is a  mycobacterium  or an antibiotic resistant bacterium.  
     
     
         22 . The method according to  claim 9  wherein said bacterium is a  mycobacterium  or an antibiotic resistant bacterium.  
     
     
         23 . The method according to  claim 15  wherein said microorganism is a  mycobacterium  or an antibiotic resistant bacterium.  
     
     
         24 . The method according to  claim 18  wherein said microorganism is a  mycobacterium  or an antibiotic resistant bacterium.  
     
     
         25 . The method according to  claim 20  wherein said particle is an IgG-coated immune complex.