Peptide or protein containing a C'-D loop of the CD28 receptor family

Abstract

The invention relates to a protein or peptide comprising the C′-D loop of a member of the CD28 family, uses thereof and mAbs obtainable therefrom.

1 . A protein or peptide comprising the C′-D loop of a member of the CD28 family or containing a peptide analogous thereto or containing a mimicry compound thereto, wherein the protein is not however a member of the CD28 family.  
     
     
         2 . A peptide according to  claim 1 , wherein the ends thereof are bound to one binding position each of a substrate, wherein the binding positions of the substrate are spatially arranged with regard to each other according to the binding positions for the C′-D loop in CD28, wherein the C′-D loop or the peptide being analogous thereto is fixed in a three-dimensional configuration according to the C′-D loop in CD28, the bound C′-D loop or the peptide being analogous thereto being freely accessible for antibodies, and wherein the substrate is not a member of the CD28 family without a C′-D loop or a natural peptide being analogous thereto of the respective CD28 family member.  
     
     
         3 . A peptide or protein according to  claim 1  or  2 , comprising an amino acid sequence having seq.-ID 41, seq.-ID 1 or 5-10, but not however human CD28; seq.-ID 42, seq.-ID 2 or 12-17, but not however human CTLA-; seq.-ID 43, seq.-ID 3 or 19 -24, but not however human ICOS; or seq.-ID 44, seq.-ID 4 or 26-31, but not however human PD-1.  
     
     
         4 . A peptide or protein or mimicry compound according to  claim 1 , obtainable by one or more prospective proteins or peptides that are subjected to a binding test with one of the monoclonal antibodies (mAbs) 9D7 or 5.11A, and binding peptides or proteins are selected.  
     
     
         5 . A nucleic acid coding for a peptide according to  claim 1  or for a protein containing this peptide, with the proviso that the nucleic acid does not code for a member of the CD28 family.  
     
     
         6 . A vector comprising a nucleic acid according to  claim 5  operably linked to a suitable promotor for expression in a target cell line being transfected with the vector.  
     
     
         7 . Use of a peptide or protein or mimicry compound thereto according to  claim 1  for producing a pharmaceutical composition for the modulation of T cell proliferation.  
     
     
         8 . A method using the peptide of  claim 1 , wherein the peptide is optionally lacking the binding site for costimulatory mAbs, comprising producing mAbs which superagonistically modulate the proliferation of T cells of several to all sub-groups, wherein a non-human mammal is immunized with the protein or peptide or the mimicry compound thereto, wherein from the non-human mammal cells are taken, and hybridoma cells are produced from the cells, and wherein the obtained hybridoma cells are selected such that in their culture supernatant mAbs are contained which bind to the C′-D loop of the peptide or protein or to the mimicry compound thereto.  
     
     
         9 . A method of screening for the identification of substances superagonistically modulating the proliferation of T cells of several to all sub-groups comprising using the peptide of  claim 1 , wherein the peptide is optionally lacking the binding site for costimulating mAbs, and a prospective substance or a mixture of prospective substances is subjected to a binding assay with the peptide, and wherein substances binding to the peptide are selected.  
     
     
         10 . Hybridoma cells producing mAbs binding to a peptide according to  claim 1 , wherein the cells have DSM numbers DSM ACC2531 (9D7 or 9D7G3H11) or DSM ACC2530 (5.11A or 5.11A1C2H3).  
     
     
         11 . mAbs obtainable from hybridoma cells according to  claim 10  or mAbs which are coded at least partially by one or more of the sequences having seq.-ID nos. 33, 35, 37 and/or 39, or mAbs which contain or consist of one or more sequences having seq.-ID nos. 34, 36, 38 and/or 40 or of  FIG. 10  or sequences being homologous thereto.  
     
     
         12 . Use of a mAb according to  claim 11  or of a mimicry compound thereto for producing a pharmaceutical composition for the treatment of diseases with pathologically reduced CD4 T cell counts.  
     
     
         13 . Use of a mAb according to  claim 11  or of a mimicry compound thereto for producing a pharmaceutical composition for the treatment following stem cell transplantations after chemo or radio therapy of leukemic diseases.  
     
     
         14 . Use of a mAb according to  claim 11  or of a mimicry compound thereto for producing a pharmaceutical composition for multiplying and/or qualitatively influencing immune reactions after vaccinations.  
     
     
         15 . Use of a mAb according to  claim 11  or of a mimicry compound thereto for producing a pharmaceutical composition for the treatment of autoimmune-inflammatory diseases.  
     
     
         16 . Use of a substance obtainable from a screening method according to  claim 9  for producing a pharmaceutical composition for the treatment of diseases with pathologically reduced CD4 T cell counts.  
     
     
         17 . The use of  claim 16 , wherein the diseases include AIDS.  
     
     
         18 . Use of a substance obtainable from a screening method according to  claim 9  for producing a pharmaceutical composition for the treatment following stem cell transplantations after chemo or radio therapy of leukemic diseases.  
     
     
         19 . Use of a substance obtainable from a screening method according to  claim 9  for producing a pharmaceutical composition for multiplying and/or qualitatively influencing reactions after vaccinations.  
     
     
         20 . Use of a substance obtainable from a screening method according to  claim 9  for producing a pharmaceutical composition for the treatment of autoimmune-inflammatory diseases.