High affinity TCR proteins and methods
AssigneeThe Board of Trustees of the University of Illinois
InventorsDavid M. Kranz, K. Dane Wittrup, Phillip D. Holler
Life of this patent
Estimating the term…
Abstract
T cell receptors (TCRS) that have higher affinity for a ligand than wild type TCRs are provided. These high affinity TCRs are formed by mutagenizing a T cell receptor protein coding sequence to generate a variegated population of mutants of the T cell receptor protein coding sequence; transforming the T cell receptor mutant coding sequence into yeast cells; inducing expression of the T cell receptor mutant coding sequence on the surface of yeast cells; and selecting those cells expressing T cell receptor mutants that have higher affinity for the peptide/MHC ligand than the wild type T cell receptor protein. The high affinity TCRs can be used in place of an antibody or single chain antibody.
Claims13
A method for using high affinity TCRs to identify ligands comprising:
- labeling high affinity TCRs;
- contacting said labeled TCRs with peptide/MHC ligands;
- identifying the ligand with which the labeled TCR is bound, wherein said label is selected from the group consisting of:
- fluorescent compounds, chemiluminescent compounds, radioisotopes and chromophores.
A method of using high affinity TCRs to bind to a selected peptide/MHC ligand comprising:
- labeling said high affinity TCRs that binds to the selected peptide/MHC ligand with a label;
- contacting said labeled high affinity TCRs with cells containing MHC molecules, wherein said label is selected from the group consisting of:
- fluorescent compounds, chemiluminescent compounds, radioisotopes and chromophores.
A method for using high affinity TCRs as diagnostic probes for specific peptide/MHC molecules on surfaces of cells comprising:
- labeling high affinity TCRs that binds to specific peptide/MHC ligands with a label;
- contacting said TCRs with cells;
- detecting said label.
A method for using high affinity TCRs that bind to pMHCs for diagnostic tests comprising:
- labeling the high affinity TCR with a detectable label;
- contacting said labeled high affinity TCR with cells;
- detecting the label.
A method for using high affinity T Cell Receptors (TCRs) to detect ligands comprising the steps of:
- labeling high affinity TCRs;
- contacting said labeled TCRs with peptide/MHC ligands;
- detecting the presence of the label thereby detecting the ligand to which the labeled TCR is bound wherein the high affinity TCR carries one or more mutations in a CDR.
Dependencies are inferred from the claim text.