TCRs
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T cell receptors (TCRs) are molecules of the adaptive immune system, similar to antibodies, that specifically bind peptide antigens loaded onto MHC molecules on the cell surface, and are of high interest as soluble and cell-based immunotherapeutics.
TCR engineering for high affinity and specificity
To enhance their targeting and therapeutic capabilities, we have engineered several TCRs to improve their pMHC affinities by up to 100-400-fold. In collaboration with the Baker laboratory at Notre Dame, the structure of our high affinity TCR engineered to better target a tumor antigen was solved. We are working to design the affinity of other TCRs and to alter and redirect antigen specificities.
Modeling TCR recognition
We are also making major strides toward a predictive understanding of TCR-pMHC recognition, having developed the first TCR-pMHC docking algorithm, TCRFlexDock. This was validated on a benchmark of 20 unbound TCR-pMHC test cases, and was also recently applied to predict TCR recognition of MHC-like molecules CD1 and MR1 bound to various lipid and small molecule antigens.