Patent ID: 6900024

Claim:
A method of preparing and identifying an altered T cell receptor ligand that is a weak agonist for T cells, said weak agonist being defined as increasing a T cell effector response evoked by an unaltered T cell receptor ligand while not increasing another T cell effector response evoked by the same unaltered T cell receptor ligand, wherein said altered T cell receptor ligand comprises an MHC molecule and a peptide, wherein the peptide is altered by the replacement of at least one amino acid residue, and wherein said increasing a T cell effector response and said not increasing another T cell effector response is not attributable to the absence of at least one essential co-stimulatory signal provided by viable antigen presenting cells (APC), which method comprises: (a) identifying an unaltered T cell receptor ligand comprising an unaltered peptide which binds to an unaltered MHC molecule to form a complex that can evoke T cell effector responses; (b) preparing altered peptides by determining by substitution those amino acids which, when present at each position of said peptide do not prevent formation of the peptide:MHC complex; (c) binding each of the altered peptides to unaltered MHC to form a plurality of candidate altered T cell receptor ligands; (d) screening said candidate altered T cell receptor ligands for the ability to increase a T cell effector response evoked by the unaltered T cell receptor ligand while not increasing another T cell effector response evoked by the same unaltered T cell receptor ligand to identify a candidate weak agonist; and (e) screening the candidate weak agonist identified in step (d) to identify a ligand wherein said increasing a T cell effector response and said not increasing another T cell effector response is not attributable to the absence of at least one essential co-stimulatory signal provided by viable antigen presenting cells (APC), and wherein said ligand is identified.