Methods and compositions for generating an immune response by inducing cd40 and pattern recognition receptors and adaptors thereof

Abstract

Provided are methods for activating an antigen-presenting cell and eliciting an immune response by inducing pattern recognition receptor activity, and CD40 activity. Also provided are methods for activating an antigen-presenting cell and eliciting an immune response by inducing CD40 activity without prostaglandin E2. Also provided are methods for activating an antigen-presenting cell and eliciting an immune response by inducing an inducible chimeric molecule comprising a region of a pattern recognition receptor or an adaptor thereof.

1 - 23 . (canceled) 
     
     
         24 . A nucleic acid comprising a polynucleotide that encodes a chimeric protein, wherein the chimeric protein comprises:
 (a) a ligand binding region comprising a FKBP12(v36) polypeptide;   (b) a MyD88 polypeptide region; and   (c) a CD40 cytoplasmic polypeptide region lacking the CD40 extracellular domain.   
     
     
         25 . The nucleic acid of  claim 24 , wherein the FKBP ligand binding region comprises two FKBP12(v36) polypeptides. 
     
     
         26 . The nucleic acid of  claim 24 , wherein the FKBP ligand binding region comprises Fv′Fvls. 
     
     
         27 . The nucleic acid of  claim 24 , wherein the CD40 cytoplasmic polypeptide region is encoded by a polynucleotide sequence in SEQ ID NO: 1. 
     
     
         28 . The nucleic acid of  claim 24 , wherein the nucleic acid is a viral vector. 
     
     
         29 . The nucleic acid of  claim 24 , wherein the nucleic acid is a plasmid vector. 
     
     
         30 . The nucleic acid of  claim 24 , wherein the ligand binding region is amino terminal to the CD40 cytoplasmic polypeptide region of the chimeric protein. 
     
     
         31 . The nucleic acid of  claim 24 , wherein the nucleic acid comprises a promoter sequence operably linked to the polynucleotide. 
     
     
         32 . The nucleic acid of  claim 24 , wherein the chimeric protein comprises a membrane targeting region. 
     
     
         33 . The nucleic acid of  claim 32 , wherein the FKBP ligand binding region comprises two FKBP12(v36) polypeptides. 
     
     
         34 . The nucleic acid of  claim 32 , wherein the FKBP ligand binding region comprises Fv′Fvls. 
     
     
         35 . The nucleic acid of  claim 32 , wherein the CD40 cytoplasmic polypeptide region is encoded by a polynucleotide sequence in SEQ ID NO: 1. 
     
     
         36 . The nucleic acid of  claim 32 , wherein the nucleic acid is contained within a viral vector. 
     
     
         37 . The nucleic acid of  claim 32 , wherein the nucleic acid is contained within a plasmid vector. 
     
     
         38 . The nucleic acid of  claim 32 , wherein the ligand binding region is amino terminal to the CD40 cytoplasmic polypeptide region of the chimeric protein. 
     
     
         39 . The nucleic acid of  claim 32 , wherein the nucleic acid comprises a promoter sequence operably linked to the polynucleotide. 
     
     
         40 . The nucleic acid of  claim 32 , wherein the membrane targeting region is a myristoylation targeting region.