Immunomodulatory Peptides Derived from Heat Shock Proteins and Uses Thereof

Abstract

A method of modulating an immune response in a subject is disclosed. The invention is based on the discovery that an effective therapeutic strategy for ameliorating the inflammation-related symptoms of an immune-mediated disease, such as arthritis, can be achieved by modulation of the underlying immune response itself, rather than by merely addressing the resulting inflammation. This strategy can be used to regulate the inflammatory response and is applicable to a variety of contexts in which immune modulation is desired, such as mucosal tolerization, DNA vaccination, anergy induction, active immunization, and ex vivo modulation of antigen-specific T cells. In one embodiment, the method comprises administering to the subject a bacterial dnaJ peptide or a human homolog or a non-homologous human isoform thereof.

1 . A method of modulating an immune response in a subject, the method comprising administering an immunogenic peptide portion of a dnaJ heat shock protein (hsp) to the subject, thereby modulating an immune response in the subject. 
     
     
         2 . The method of  claim 1 , wherein the dnaJ hsp is a bacterial dnaJ hsp. 
     
     
         3 - 65 . (canceled) 
     
     
         66 . The method of  claim 1 , wherein the dnaJ hsp is a human dnaJ hsp. 
     
     
         67 . The method of  claim 1 , wherein the peptide is selected from the group consisting of SEQ ID NOs: 1 to 18, 20 to 26, and any combination thereof. 
     
     
         68 . The method of  claim 1 , wherein the peptide is SEQ ID NO: 19 in combination with any one or more of SEQ ID NOs: 1 to 18, 20 to 26. 
     
     
         69 . The method of  claim 1 , wherein the peptide is administered intradermally, subcutaneously, intramuscularly, or mucosally. 
     
     
         70 . The method of  claim 1 , wherein the subject has an immunological disorder. 
     
     
         71 . The method of  claim 70 , wherein the immunological disorder is an arthritis. 
     
     
         72 . The method of  claim 71 , wherein the arthritis is articular juvenile idiopathic arthritis. 
     
     
         73 . A method of modulating immunoeffector cell responsiveness, the method comprising contacting immunoeffector cells with a peptide portion of a dnaJ heat shock protein (hsp) to the subject. 
     
     
         74 . The method of  claim 73 , wherein the peptide is selected from the group consisting of SEQ ID NOs: 1 to 18, 20 to 26, and any combination thereof. 
     
     
         75 . The method of  claim 73 , wherein the peptide is SEQ ID NO: 19 in combination with any one or more of SEQ ID NOs: 1 to 18, 20 to 26. 
     
     
         76 . The method of  claim 73 , wherein contacting the immunoeffector cells comprises administering the peptide to a subject, wherein said contacting occurs in vivo. 
     
     
         77 . The method of  claim 73 , wherein contacting the immunoeffector cells is performed in vitro. 
     
     
         78 . The method of  claim 73 , further comprising administering the immunoeffector cells to a subject, thereby modulating an immune response in the subject. 
     
     
         79 . The method of  claim 78 , wherein the immunoeffector cells are autologous with respect to the subject. 
     
     
         80 . The method of  claim 78 , wherein the immunoeffector cells are allogeneic with respect to the subject. 
     
     
         81 . The method of  claim 73 , wherein the immunoeffector cells are T cells. 
     
     
         82 . The method of  claim 73 , further comprising contacting the immunoeffector cells with an immunoadjuvant. 
     
     
         83 . The method of  claim 82 , wherein the immunoadjuvant is a cytokine.