A systems view of recognition by the T cell receptor provides multiple opportunities for rational therapeutic interventions in cancer, infection and autoimmunity

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• Andrew Sewell, University of Cardiff
• Friday 22 November 2013, 13:00-14:00
• Sackler Lecture Theater on level 7 of the CIMR (Cambridge Institute for Medical Research).

If you have a question about this talk, please contact Dr Tennie Videler.

Andrew Sewell, hosted by John Trowsdale

Clonal selection theory proposed that individual T-cells are specific for a single peptide–MHC antigen. However, the repertoire of alpha-beta T cell receptors (TCRs) is dwarfed by the vast array of potential foreign peptide–MHC complexes and a comprehensive system requires each T-cell to recognize numerous peptides and thus be crossreactive. This compromise on specificity has profound implications because the chance of any ligand being an optimal fit for its cognate TCR is small as there will almost always be more potent agonists. Furthermore, any TCR raised against a specific peptide–MHC in vivo can only be the best available solution from the naïve T-cell pool and is unlikely to be the best possible solution from the substantially greater number of TCRs that could theoretically be produced. This ‘systems view’ of TCR recognition allows multiple avenues for manipulation of T-cell immunity. In this talk I hope to explore how enhanced T cell receptors and altered peptide [or non-peptide] TCR ligands can be used in immunotherapy.

This talk is part of the Immunology in medicine series.

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