Fig. 3: Co-crystal structure of a TRACeR–MHC complex reveals an extended antigen recognition interface to guide specificity enhancement.
From: Targeting peptide antigens using a multiallelic MHC I-binding system
a, The asymmetric unit of \({\rm{TRACeR}}_{\rm{MHC}\;{\rm{I}},\,{\rm{A02}}}^{{\rm{NY}}-{\rm{ESO}}-1}\) engaging two pMHC I molecules. Domain-swapped TRACeR, yellow and green; MHC I heavy chain, gray; MHC I light chain, orange; NY-ESO-1 peptide, cyan. b, \({\rm{TRACeR}}_{\rm{MHC}\;{\rm{I}},\,{\rm{A02}}}^{{\rm{NY}}-{\rm{ESO}}-1}\) helices binding to pMHC I, with the ___location of the ARE. c, Footprint of \({\rm{TRACeR}}_{\rm{MHC}\;{\rm{I}},\,{\rm{A02}}}^{{\rm{NY}}-{\rm{ESO}}-1}\) on pMHC I. pMHC I interface atoms within 5-Å distance from TRACeR, red; small hydrophobic residues on MHC groove that TRACeR docks on, yellow. Sequence conservation for the TRACER-contacting MHC I residues on common HLA alleles are shown as a sequence logo. d, Open-book view of MHC I–TRACeR interface showing a high level of shape complementarity. e, The interacting residues between \({\rm{TRACeR}}_{\rm{MHC}\;{\rm{I}},\,{\rm{A02}}}^{{\rm{NY}}-{\rm{ESO}}-1}\) and NY-ESO-1 peptide. TRACeR residues, green and yellow; peptide, cyan. f, Refined set of interfacial residue positions to achieve better specificity for P7 and P8. Positions included in the original library containing AREs in library 2 are shown as yellow spheres; new positions are shown in salmon. g, SSM on the five key peptide residues corresponding to the refined TRACeR specificity. The S1V peptide failed to synthesize and was not included in the library (filled with gray).
