Immunoregulatory structures from normally occuring proteins

Abstract

The present invention relates to isolated protein sequences that correspond to cell binding peptides, fragments, neo-structures and/or neo-epitopes of a normally occurring serum protein present in human tissue, wherein the peptide, fragment, neo-structure and/or neo-epitope has an immunoregulatory activity and is the result of either an enhanced proteolytic activity and/or conformational changes in a tissue, or a malignant tumour. In the present patent application, a common structure of several of these peptides, fragments, neo-structures and/or neo-epitopes, having immunoregulatory activity by binding to receptors on immune cells, has been identified. The present invention further also relates to monoclonal and/or polyclonal antibodies directed to a cell binding fragment of a normally occurring serum protein present in human tissue, as described above.

1 .- 26 . (canceled) 
     
     
         27 . A method of using an isolated neo-epitope of albumin as an immunoinhibitor in an inflammatory condition or disease,
 the isolated neo-epitope comprising an amino acid sequence selected from the group consisting of: LVNEVTEFAK (SEQ ID NO:104), SLHTLFGDK (SEQ ID NO:84), LCTVATLR (SEQ ID NO:85), ETYGEMADCCAK (SEQ ID NO:86), YLYEIAR (SEQ ID NO:87), LDELRDEGK (SEQ ID NO:88), YICENQDSISSK (SEQ ID NO:89), LKECCEKPLLEK (SEQ ID NO:90), HPDYSVVLLLR (SEQ ID NO:91), CCAAADPHECYAK (SEQ ID NO:92), QNCELFEQLGEYK (SEQ ID NO:93), FQNALLVR (SEQ ID NO:94), CCTESLVNR (SEQ ID NO:95), and AVMDDFAAFVEK (SEQ ID NO:96),   the method comprising administering the isolated neo-epitope to a subject having an inflammatory condition or disease.   
     
     
         28 . The method of  claim 27 , wherein the isolated neo-epitope of albumin comprises the amino acid sequence of YLYEIAR (SEQ ID NO: 87) 
     
     
         29 . The method of  claim 27 , wherein the isolated neo-epitope of albumin comprises the amino acid sequence of KYLYEIAR (SEQ ID NO: 115). 
     
     
         30 . The method of  claim 27 , wherein the isolated neo-epitope of albumin comprises the amino acid sequence of KLVNEVTEFAKT (SEQ ID NO: 106). 
     
     
         31 . The method of  claim 27 , wherein the isolated neo-epitope of albumin comprises the amino acid sequence of KLDELRDEGKAS (SEQ ID NO: 112). 
     
     
         32 . The method of  claim 27 , wherein the isolated neo-epitope of albumin comprises the amino acid sequence of ELFEQLGEYKFQNALLVR (SEQ ID NO: 147). 
     
     
         33 . The method of  claim 27 , wherein the isolated neo-epitope of albumin binds to an immune cell. 
     
     
         34 . The method of  claim 27 , wherein the inflammatory condition or disease is selected from the group consisting of: psoriasis, T-cell lymphoma, allograft rejection, GVH, ischemia-reperfusion injury, chronic inflammatory diseases, and an autoimmune disease. 
     
     
         35 . A method of using an isolated neo-epitope of albumin as an immunoinhibitor in an inflammatory condition or disease,
 the isolated immune cell binding peptide comprising the amino acid sequence NEETFLKKYLYE (SEQ ID NO: 110),   the method comprising administering the isolated neo-epitope of albumin to a subject having an inflammatory condition or disease.   
     
     
         36 . The method of  claim 35 , wherein the inflammatory condition or disease is selected from the group consisting of psoriasis, T-cell lymphoma, allograft rejection, GVH, ischemia-reperfusion injury, chronic inflammatory diseases and an autoimmune disease. 
     
     
         37 . A monoclonal antibody directed to an immune cell binding neo-epitope of albumin, the isolated immune cell binding neo-epitope comprising an amino acid sequence selected from the group consisting of: LVNEVTEFAK (SEQ ID NO: 104), SLHTLFGDK (SEQ ID NO:84), LCTVATLR (SEQ ID NO:85), ETYGEMADCCAK (SEQ ID NO:86), YLYEIAR (SEQ ID NO:87), LDELRDEGK (SEQ ID NO:88), YICENQDSISSK (SEQ ID NO:89), LKECCEKPLLEK (SEQ ID NO:90), HPDYSVVLLLR (SEQ ID NO:91), CCAAADPHECYAK (SEQ ID NO:92), QNCELFEQLGEYK (SEQ ID NO:93), FQNALLVR (SEQ ID NO:94), CCTESLVNR (SEQ ID NO:95), and AVMDDFAAFVEK (SEQ ID NO:96). 
     
     
         38 . The monoclonal antibody of  claim 37 , wherein the immune cell binding neo-epitope of albumin comprises the amino acid sequence YLYEIAR (SEQ ID NO: 87).