The TCR constructs used by Juno are selected by screening healthy donors for naturally-occurring high-affinity TCRs against a MHC/peptide combination of interest (Company Pipeline Juno, NOV 25, 2014, View Source [SID:1234501011]). Depending on the binding affinity of the selected TCR construct, it is either used directly or modified by mutating a specific region, the hypervariable domain, of the TCR binding pocket to create a higher affinity construct. Due to the variability of MHC types across the human population, different TCRs will be required for various segments of the population.

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