Structure - activity relationships for novel engineered high-affinity T cell receptors

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T cell receptors are related to antibodies, but they recognise short processed peptide antigens presented on the cell-surface by specialised proteins. They also have relatively low affinity. Recently, I have succeeded in engineering T cell receptors to have up to 1,000,000 times higher affinity by a process involving display by bacteriophage. These high-affinity T cell receptors have similar characteristics to monoclonal antibodies and have many potential biomedical applications in the treatment of viral infections, cancer and autoimmune diseases. High affinity is generated by several mutations in the T cell receptor sequence but it is currently very unclear exactly how high affinity is generated by these mutations. In this project, I will examine these mutations on an individual basis to build up 'structure - activity relationships' for two published high-affinity T cell receptors. This will provide an insight into how they work and could potentially enable computer prediction of high affinity for T cell receptors in the future.