High affinity TCR proteins and methods

A method of using high affinity TCRs to bind to a selected peptide/MHC ligand comprising:

• labeling said high affinity TCRs with a label that binds to the selected peptide/MHC ligand;
• contacting said labeled high affinity TCRs with cells containing MHC molecules.

A method for using high affinity TCRs as diagnostic probes for specific peptide/MHC molecules on surfaces of cells comprising:

• labeling high affinity TCRs with a label that binds to specific peptide/MHC ligands;
• 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 high affinity TCR with cells;
• detecting the label.

The method for blocking autoimmune destruction of cells comprising:

• contacting TCRs with high affinity for the site recognized by the T lymphocytes on the surface of a target cell with cells, whereby the autoimmune destruction of cells is blocked.

The method for using high affinity TCRs to treat disease comprising:

• coupling a TCR having a high affinity for a neoplastic cell surface marker with a therapeutic compound;
• and
• contacting said TCR with cells.

A method of using high affinity TCRs to inactivate pathogens comprising:

• binding a molecule which is toxic to the pathogen to the high affinity TCR;
• and contacting said TCR with cells that express said pathogen.

Soluble T cell receptors (TCRs) having higher affinity for a ligand than wild type TCRs.

A library of T cell receptor proteins displayed on the surface of yeast cells which have higher affinity for the peptide/HC ligand than the wild type T cell receptor protein, wherein said library is 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.