Fig. 4: Engineered monomeric TRACeR-I shows multi-HLA allelic compatibility. | Nature Biotechnology

Fig. 4: Engineered monomeric TRACeR-I shows multi-HLA allelic compatibility.

From: Targeting peptide antigens using a multiallelic MHC I-binding system

Fig. 4: Engineered monomeric TRACeR-I shows multi-HLA allelic compatibility.

a, Rewiring scheme to connect domain-swapped TRACeR into a monomer. b, Model of rewired TRACeR on MHC I. c, In vitro tumor cell cytotoxicity assays with \({\rm{TRACeR}}_{\rm{MHC}\;{\rm{I}},\,{\rm{A02}}}^{{\rm{NY}}-{\rm{ESO}}-1}\)CAR-T cells derived from primary CD8+ T cells from two donors. Percentage of live tumor cells cocultured with engineered T cells were normalized to those cocultured with untransduced T cells. Each data point represents technical replicates from five experiments, plotted as the mean ± s.d. d. BLI affinity measurements of the rewired \({\rm{TRACeR}}_{\rm{MHC}\;{\rm{I}},\,{\rm{A02}}}^{{\rm{NY}}-{\rm{ESO}}-1}\). e, Open-book view of the TRACeR interface with library positions colored in salmon and the peptide colored in cyan. f, TRACeR-I binding to a panel of diverse disease-relevant epitopic peptides presented by diverse HLAs. The final enrichment round before NGS is shown; multiple sequences were present in the pool. Staining concentration: on target, 25 nM tetramer concentration; off target, 100 nM tetramer concentration. g, Rosetta models of the most enriched TRACeR clone from NGS for each pMHC I target.

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