Structural Engineering of pMHC Reagents for T Cell Vaccines and Diagnostics

Vesselin Mitaksov, Steven M. Truscott, Lonnie Lybarger, Janet M. Connolly, Ted H. Hansen, Daved H H. Fremont

Research output: Contribution to journalArticle

32 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)909-922
Number of pages14
JournalChemistry and Biology
Volume14
Issue number8
DOIs
StatePublished - Aug 24 2007

Keywords

  • CHEMBIO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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  • Cite this

    Mitaksov, V., Truscott, S. M., Lybarger, L., Connolly, J. M., Hansen, T. H., & Fremont, DH. H. (2007). Structural Engineering of pMHC Reagents for T Cell Vaccines and Diagnostics. Chemistry and Biology, 14(8), 909-922. https://doi.org/10.1016/j.chembiol.2007.07.010