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PDBsum entry 2qrt
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Immune system
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PDB id
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2qrt
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References listed in PDB file
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Key reference
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Title
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Structural engineering of pmhc reagents for t cell vaccines and diagnostics.
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Authors
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V.Mitaksov,
S.M.Truscott,
L.Lybarger,
J.M.Connolly,
T.H.Hansen,
D.H.Fremont.
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Ref.
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Chem Biol, 2007,
14,
909-922.
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PubMed id
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Abstract
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MHC class I peptide complexes (pMHC) are routinely used to enumerate T cell
populations and are currently being evaluated as vaccines to tumors and specific
pathogens. 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.
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