HA-1 epitopes and uses thereof

Abstract

Peptide sequences constituting T-cell epitopes of minor Histocompatibility antigen, HA-1. HA-1 is associated with Graft versus Host Disease. The peptides and their derivatives find many uses, for instance, in bone marrow transplantation, organ transplantation and in treatment of leukemia and non-hematopoietic tumors. The peptide and/or its derivatives can be incorporated in vaccines, in pharmaceutical formulations and they can be used in diagnostic test kits. HA-1 is expressed by non-hematopoietic tumor cells. While absent in normal epithelial cells, tumor cells and tumor cell lines, particularly from epithelial origin, express HA-1 and are recognized by HA-1 cytotoxic T-cells. The invention provides means and methods for HA-1 specific immunotherapy for HA-1-positive patients with non-hematopoietic tumor cells.

1 . A peptide characterized in being immunogenic and obtainable from a minor Histocompatibility antigen HA-1, said peptide further characterized by comprising a sequence selected from the group of sequences consisting of VLXDDLLEA (SEQ ID NO:1), KECVLXDDL (SEQ ID NO:3), combinations thereof, and a derivative of any thereof having similar functional or immunological properties, wherein X represents a histidine or an arginine residue. 
     
     
         2 . The peptide of  claim 1 , wherein the sequence is VLHDDLLEA (SEQ ID NO:2). 
     
     
         3 . The peptide of  claim 1 , wherein the sequence is KECVLHDDL (SEQ ID NO:4). 
     
     
         4 . A preparation comprising the peptide of  claim 1 . 
     
     
         5 . A preparation comprising the peptide of  claim 2 . 
     
     
         6 . A preparation comprising the peptide of  claim 3 . 
     
     
         7 . A method of inducing tolerance in a subject to transplants to prevent rejection and/or Graft versus Host disease or a method treating (auto)immune disease in a subject, said method comprising:
 administering the preparation of  claim 4  to the subject.   
     
     
         8 . A method for elimination of a group of hematopoietic cells, said method comprising:
 presenting the peptide of  claim 1  in the context of HLA class-I, wherein said elimination is induced directly or indirectly by specific recognition of the peptide in the context of HLA class-I.   
     
     
         9 . An analog of the peptide of  claim 1 , wherein said analog is an antagonist for the activity of a T-cell recognizing the peptide. 
     
     
         10 . A process for producing antibodies, T-cell receptors, anti-idiotypic B-cells, T-cells, or mixtures of any thereof, said process comprising:
 immunizing a mammal with the peptide of  claim 1 ; and   harvesting antibodies, T-cell receptors, anti-idiotypic B-cells, T-cells, or mixtures of any thereof from the mammal.   
     
     
         11 . Antibodies, T-cell receptors, B-cells, T-cells, and or mixtures of any thereof obtainable by the process of  claim 10 . 
     
     
         12 . A process for generating a cytotoxic T-cell against a minor antigen, said method comprising:
 contacting a cell selected from the group of a hematopoietic cell and a dendritic cell with the peptide of  claim 1 , thus generating a cytotoxic T-cell against the minor antigen.   
     
     
         13 . The process of  claim 12 , wherein the cell is contacted with the peptide in the context of HLA-B60. 
     
     
         14 . The process of  claim 12 , wherein the cell is a dendritic cell. 
     
     
         15 . The process of  claim 12 , wherein the cell is a hematopoietic cell negative for said minor antigen. 
     
     
         16 . The process of  claim 12 , wherein said minor antigen is HA-1. 
     
     
         17 . The process of  claim 12 , wherein the contacting is carried out ex vivo. 
     
     
         18 . The process of  claim 12 , wherein said cytotoxic T-cell includes a suicide gene. 
     
     
         19 . The process of  claim 12 , wherein said cytotoxic T-cell is immortalized. 
     
     
         20 . A cytotoxic T-cell obtainable by the process  claim 12 . 
     
     
         21 - 48 . (canceled)