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 . An isolated nucleic acid comprising a promoter operatively linked to a polynucleotide, in order from 5′ to 3′, encoding a chimeric protein, wherein the chimeric protein comprises:
 (a) 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, 
 (b) a CD40 cytoplasmic polypeptide region lacking the CD40 extracellular domain; and 
 (c) at least two FKBP12 multimeric ligand-binding regions. 
 
     
     
         18 . The isolated nucleic acid of  claim 17 , wherein each of said at least two FKBP12 multimeric ligand-binding regions bind to AP1903 or AP20187. 
     
     
         19 . The isolated nucleic acid of  claim 17 , wherein each of said at least two FKBP12 multimeric ligand-binding regions comprise an amino acid substitution at position 36. 
     
     
         20 . The isolated nucleic acid of  claim 17 , wherein each of said at least two FKBP12 multimeric ligand-binding region comprises a FKBP12(V36) polypeptide. 
     
     
         21 . The isolated nucleic acid of  claim 17 , wherein the nucleic acid is contained within an isolated vector. 
     
     
         22 . The nucleic acid of  claim 21 , wherein the nucleic acid is contained within an isolated viral vector. 
     
     
         23 . The nucleic acid of  claim 21 , wherein the nucleic acid is contained within an isolated plasmid vector. 
     
     
         24 . An isolated cell transduced or transfected with a vector of  claim 21 . 
     
     
         25 . A method for activating a cell, comprising transfecting or transducing the cell with a vector of  claim 21 , and contacting the transfected or transduced cell with a ligand that binds to the ligand binding region, whereby the cell is activated. 
     
     
         26 . The method of  claim 25 , wherein the ligand is AP1903 or AP20187.