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Herein, we describe the structures of three generations of single-chain pMHC progressively designed for the optimal presentation of covalently associated epitopes. Our ultimate design employs a versatile disulfide trap between an invariant MHC residue and a short C-terminal peptide extension. This general strategy is nondisruptive of native pMHC conformation and T cell receptor engagement. Indeed, cell-surface-expressed MHC complexes with disulfide-trapped epitopes are refractory to peptide exchange, suggesting they will make safe and effective vaccines. Furthermore, we find that disulfide-trap stabilized, recombinant pMHC reagents reliably detect polyclonal CD8 T cell populations as proficiently as conventional reagents and are thus well suited to monitor or modulate immune responses during pathogenesis.","bibjson":{"author":[{"initials":"V","lastname":"Mitaksov","name":"Mitaksov V"},{"initials":"SM","lastname":"Truscott","name":"Truscott SM"},{"initials":"L","lastname":"Lybarger","name":"Lybarger L"},{"initials":"JM","lastname":"Connolly","name":"Connolly JM"},{"initials":"TH","lastname":"Hansen","name":"Hansen TH"},{"initials":"DH","lastname":"Fremont","name":"Fremont DH"}],"identifier":[{"id":"10.1016/j.chembiol.2007.07.010","type":"doi"},{"id":"17719490","type":"pubmed"}],"issue":["8"],"journal":{"iso_abbreviation":"Chem. Biol.","name":""},"pages":["909-22"],"title":"Structural engineering of pMHC reagents for T cell vaccines and diagnostics.","type":"article","url":"https://www.sciencedirect.com/science/article/abs/pii/S1074552107002499","volume":["14"],"year":[2007]},"in_pmc":"N","in_pmce":"Y","open_access":"N"},"resolution":"2.00","same_as":{"pdbe":{"url":"https://www.ebi.ac.uk/pdbe/entry/pdb/2qrs"},"rcsb":{"url":"https://www.rcsb.org/structure/2qrs"}},"species":{"common_name":"Mouse","match_type":"histo:assign_species","scientific_name":"Mus musculus","slug":"mus_musculus"},"tcr":null,"title":"Single chain construct of H2-Kb binding \"None\" at 2.00&#8491; resolution","unique_chain_count":1}}
