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, 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 seq.-ID 41, seq.-ID 1 or 5-10, not however human CD28, seq.-ID 42, seq.-ID 2 or 12-17, not however human CTLA-4, seq.-ID 43, seq.-ID 3 or 19-24, not however human ICOS, or seq.-ID 44, seq.-ID 4 or 26-31, not however human PD-1.  
     
     
         4 . A peptide or protein or mimicry compound according to one of  claims 1  to  3 , obtainable by that one or more prospective proteins or peptides 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 one of  claims 1  to  4  or for a protein containing this peptide, not however coding 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 one of  claims 1  to  4  for producing a pharmaceutical composition for the modulation of the T cell proliferation.  
     
     
         8 . Use of a peptide according to one of  claims 1  to  4  or of a protein containing this peptide or of a mimicry compound thereto, optionally lacking the binding site for costimulatory mAbs, in a method for 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 thus 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 . Use of a peptide according to one of  claims 1  to  4  or of a protein containing this peptide or of a mimicry compound thereto, optionally lacking the binding site for costimulatory mAbs, in a screening method for the identification of substances superagonistically modulating the proliferation of T cells of several to all sub-groups, wherein a prospective substance or a mixture of prospective substances is subjected to a binding assay with the peptide or protein or mimicry compound, and wherein substances binding to the peptide or protein or mimicry compound are selected, in particular mAbs and/or mimicry compounds.  
     
     
         10 . Hybridoma cells producing mAbs binding to a peptide or protein according to one of  claims 1  to  4 , in particular as filed under the 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 seq.-ID 33, 35, 37 and/or 39, or mAbs which contain or consist of one or more sequences seq.-ID 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 or 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, in particular AIDS.  
     
     
         13 . Use of a mAb according to  claim 11  or of a mimicry compound thereto or 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.  
     
     
         14 . Use of a mAb according to  claim 11  or of a mimicry compound thereto or of a substance obtainable from a screening method according to  claim 9  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 or of a substance obtainable from a screening method according to  claim 9  for producing a pharmaceutical composition for the treatment of autoimmune-inflammatory diseases.