Procedures and compositions for the inhibition of modulation of the costimulatory pathway of T lymphocytes by a pathogen

摘要

An isolated and purified peptide consisting of: (a) a peptide comprising an amino acid sequence that is a dimer interface of a member of the T-lymphocyte costimulatory pathway selected from the dimer interface within human CD28, human CTLA4, Human ICOS and human PD-1, said amino acid sequence being selected from amino acid residues 10-15 or 116-121 of SEQ ID NO: 19, amino acid residues 10-15 or 115-120 of SEQ ID N. : 20, amino acid residues 10-15 or 119-124 of SEQ ID NO: 21, and amino acid residues 8-13 or 110-116 of SEQ ID NO: 59, in which the peptide: ( i) is a peptide from the human CD28 dimer interface consisting of the amino acid sequence HVKGKHLCP as indicated by SEQ ID NO: 9 or the amino acid sequence SPMLVAYD as indicated by SEQ ID NO: 12; (ii) is a peptide from the human CTLA4 dimer interface consisting of the amino acid sequence YVIDPEPCP as indicated by SEQ ID NO: 14 or the amino acid sequence PAWLASS as indicated by SEQ ID NO: 15 ; (iii) is a peptide from the human ICOS dimer interface consisting of the amino acid sequence YESQLCCQL as indicated by SEQ ID NO: 16 or the amino acid sequence GEINGSAN as indicated by SEQ ID NO: 17 ; or (iv) is a peptide from the human PD-1 dimer interface consisting of the amino acid sequence RVTERRAEV as indicated by SEQ ID NO: 57 or the amino acid sequence PALLWTE as indicated by SEQ ID N. º: 58; (b) a peptide that is at least 80% homologous to the human CD28 peptide of SEQ ID NO: 9 or 12, wherein the peptide resulting from (b) maintains the ability to inhibit interaction between a member of the costimulatory pathway of T lymphocytes and a superantigen; (c) a peptide of (a) having an insert of an amino acid residue, in which the resulting peptide of (c) maintains the ability to inhibit the interaction between a member of the costimulatory pathway of T lymphocytes and a superantigen; (d) a peptide of (a), (b) or (c) that is prolonged at the N-terminus and / or the C-terminus: (i) by a lauryl-cysteine at the N-terminus and a cysteine at the C-terminus ; or (ii) by an organic residue that is not a naturally occurring or synthetic amino acid residue; or (iii) by identical hydrophobic amino acid residue (s) which may be amino acid residue (s) that occurs naturally or synthetically; or (iv) by a lysyl-palmitoyl tail, in which said tail is at the N-terminus, in which the peptide resulting from (c) maintains the ability to inhibit the interaction between a member of the costimulatory pathway of T lymphocytes and a superantigen; (e) a dimer or multimer of (a), (b), (c) or (d) in which the peptide resulting from (e) maintains the ability to inhibit the interaction between a member of the costimulatory pathway of T lymphocytes and a super antigen.