US Patent 7608410 Method of improving T cell receptors

A method of increasing the affinity and/or decreasing the off-rate of a given TCR specific for a given target pMHC, comprising creating a plurality of TCRs having an α chain CDR2 sequence and/or a β chain CDR2 sequence different from the corresponding CDR2 sequence(s) of the given TCR but having the same α and β CDR1 and CDR3 sequences as the given TCR, determining the affinity and/or off-rate of members of said plurality of TCRs for the target pMHC, and selecting one or more members having at least a 10-fold greater affinity for the target pMHC than the given TCR and/or a 10-fold slower off-rate for the target pMHC than the given TCR.