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Chem Biol. 2007 Aug;14(8):909-22.

Structural engineering of pMHC reagents for T cell vaccines and diagnostics.

Author information

1
Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.

Abstract

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.

PMID:
17719490
PMCID:
PMC3601489
DOI:
10.1016/j.chembiol.2007.07.010
[Indexed for MEDLINE]
Free PMC Article

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