Methods and compositions for generating an immune response by inducing cd40 and pattern recognition receptor adapters

Abstract

Provided are methods for activating an antigen-presenting cell and eliciting an immune response by inducing an inducible pattern recognition receptor adapter, or adapter fragment, and CD40 activity. Also provided are nucleic acid compositions comprising sequences coding for chimeric proteins that include an inducible CD40 peptide and an inducible pattern recognition receptor adapter or adapter fragment.

1 - 16 . (canceled) 
     
     
         17 . A nucleic acid comprising a promoter operatively linked to a polynucleotide encoding a chimeric protein, wherein the chimeric protein comprises
 (a) a CD40 cytoplasmic polypeptide region lacking the CD40 extracellular domain,   (b) a truncated MyD88 polypeptide lacking the TIR domain, wherein the truncated MyD88 polypeptide comprises amino acid residues 1-172 and does not include contiguous amino acid residues 173-296 of a full length native human MyD88 polypeptide; and   (c) an FKBP12 multimeric ligand-binding region.   
     
     
         18 . The nucleic acid of  claim 17 , wherein FKBP12 multimeric ligand-binding region binds to AP1903 or AP20187. 
     
     
         19 . The nucleic acid of  claim 17 , wherein the multimeric ligand-binding region comprises an FKBP12 polypeptide. 
     
     
         20 . The nucleic acid of  claim 17 , wherein the multimeric ligand-binding region comprises a FKBP12 ligand-binding region comprising an amino acid substitution at position 36. 
     
     
         21 . The nucleic acid of  claim 17 , wherein the FKBP12 multimeric ligand-binding region comprises a FKBP12(V36) polypeptide. 
     
     
         22 . The nucleic acid of  claim 17 , wherein the FKBP12 multimeric ligand-binding region comprises two FKBP12(V36) polypeptides. 
     
     
         23 . The nucleic acid of  claim 17 , wherein the nucleic acid is isolated. 
     
     
         24 . The nucleic acid of  claim 17 , wherein the ligand binding region is amino terminal to the CD40 cytoplasmic polypeptide region of the chimeric protein. 
     
     
         25 . The nucleic acid of  claim 17 , wherein the nucleic acid is contained within a vector. 
     
     
         26 . The nucleic acid of  claim 25 , wherein the nucleic acid is contained within a viral vector. 
     
     
         27 . The nucleic acid of  claim 25 , wherein the nucleic acid is contained within a plasmid vector. 
     
     
         28 . A cell transduced or transfected with a vector of  claim 25 . 
     
     
         29 . A method for activating a cell, comprising transfecting or transducing the cell with a vector of  claim 25 , and contacting the transfected or transduced cell with a ligand that binds to the ligand binding region, whereby the cell is activated. 
     
     
         30 . The method of  claim 29 , wherein the ligand is AP1903 or AP20187.