In vivo ctl elicitation by heat shock protein fusion proteins maps to a discrete domain and is cd4+ t cell-independent

Abstract

The present invention relates to a method of inducing a CD8 + CTL response to a molecule in an individual deficient in CD4 + T cells comprising administering to the individual art hsp or a portion of an ATP binding domain of an hsp joined to the molecule. In one embodiment, the present invention relates to a method of treating HIV in an individual deficient in CD4 + T cells comprising administering to the individual an hsp or a portion of an ATP binding domain of an hsp joined to the molecule. Also encompassed by the present invention is a method of inducing a CD4 + independent CTL response in an individual comprising administering to the individual a portion of an ATP binding domain of an hsp joined to the molecule. The present invention also relates to a method of inducing a CD8 + CTL response in an individual comprising administering to the individual a portion of an ATP binding domain of an hsp joined to the molecule. In addition, the present invention relates to a composition characterized by a portion of an ATP biding domain of an hsp joined to a molecule.

1 . A method of inducing an immune response that includes a CD8 +  cytotoxic T lymphocyte (CTL) response to a molecule in an individual, the method comprising administering to the individual the molecule joined to a heat shock protein or the molecule joined to an adenosinetriphosphate (ATT) binding domain of a heat shock protein or a portion thereof. 
     
     
         2 . The method of  claim 1 , wherein the individual has a deficiency of CD4 +  T cells. 
     
     
         3 . The method of  claim 1 , wherein the heat shock protein is fused to the molecule. 
     
     
         4 . The method of  claim 1 , wherein the ATP binding domain is fused to the molecule. 
     
     
         5 . The method of  claim 1 , wherein the heat shock protein is covalently bonded or chemically conjugated to the molecule. 
     
     
         6 . The method of  claim 1 , wherein the ATP binding domain, or the portion thereof, is covalently bonded or chemically conjugated to the molecule. 
     
     
         7 . The method of  claim 1 , wherein the molecule is a protein or glycoprotein. 
     
     
         8 . The method of  claim 1 , wherein the molecule is a carbohydrate or lipid. 
     
     
         9 . The method of  claim 1 , wherein the molecule is a bacterial or viral antigen. 
     
     
         10 . The method of  claim 1 , wherein the viral antigen is an antigen of the human immunodeficiency virus. 
     
     
         11 . The method of  claim 1 , wherein the molecule is a parasitic antigen. 
     
     
         12 . The method of  claim 1 , wherein the molecule is a cancer cell-associated antigen. 
     
     
         13 . The method of  claim 1 , wherein the heat shock protein, the ATP binding domain of the heat shock protein, or the portion thereof, is a mycobacterial protein. 
     
     
         14 . The method of  claim 13 , wherein the mycobacterial protein is an  M. leprae, M. bovis , or  M. tuberculosis  protein. 
     
     
         15 . The method of  claim 1 , wherein the heat shock protein, the ATP binding domain of the heat shock protein, or the portion thereof, is hsp65, hsp70, or hsp90. 
     
     
         16 . The method of  claim 1 , wherein the heat shock protein, the ATP binding domain of the heat shock protein, or the portion thereof is a mammalian protein. 
     
     
         17 . The method of  claim 16 , wherein the mammalian protein is a human protein. 
     
     
         18 . The method of  claim 1 , wherein, the portion of the ATP binding domain consists of about half of the ATP binding domain. 
     
     
         19 . The method of  claim 1 , wherein the portion of the ATP binding domain is a portion of a naturally occurring ATP binding domain in which 1-50% of the amino acid residues have been substituted; 10-40% of the amino acid residues have been substituted; or 10-20% of the amino acid residues have been substituted. 
     
     
         20 . The method of  claim 1 , wherein at least half of the substituted amino acid residues are conservative amino acid substitutions. 
     
     
         21 . The method of  claim 1 , wherein the portion of the ATP binding domain comprises amino acid residues 161-370 of  Mycobacterium tuberculosis  hsp70. 
     
     
         22 . The method of  claim 2 , wherein the individual has an acquired immune deficiency syndrome. 
     
     
         23 . A method of inducing a CD4 +  independent cytotoxic T lymphocyte response to a molecule in an individual, the method comprising administering to the individual a portion of an AFP binding domain of a heat shock protein joined to the molecule. 
     
     
         24 . The method of  claim 23 , wherein the molecule is a protein, a peptide, a glycoprotein, a carbohydrate, a viral antigen, a fungal antigen, or a parasitic antigen. 
     
     
         25 . The method of  claim 23 , wherein the heat shock protein is an hsp65, hsp70, hsp90, bacterial, mycobacterial, fungal, parasitic, or mammalian heat shock protein.