Disulfide bond engineering to trap peptides in the MHC class I binding groove

Steven M. Truscott, Lonnie Lybarger, John M. Martinko, Vesselin E. Mitaksov, David M. Kranz, Janet M. Connolly, Daved H. Fremont, Ted H. Hansen

Research output: Contribution to journalArticle

Abstract

Immunodominant peptides in CD8 T cell responses to pathogens and tumors are not always tight binders to MHC class I molecules. Furthermore, antigenic peptides that bind weakly to the MHC can be problematic when designing vaccines to elicit CD8 T cells in vivo or for the production of MHC multimers for enumerating pathogen-specific T cells in vitro. Thus, to enhance peptide binding to MHC class I, we have engineered a disulfide bond to trap antigenic peptides into the binding groove of murine MHC class I molecules expressed as single-chain trimers or SCTs. These SCTs with disulfide traps, termed dtSCTs, oxidized properly in the endoplasmic reticulum, transited to the cell surface, and were recognized by T cells. Introducing a disulfide trap created remarkably tenacious MHC/peptide complexes because the peptide moiety of the dtSCT was not displaced by high-affinity competitor peptides, even when relatively weak binding peptides were incorporated into the dtSCT. This technology promises to be useful for DNA vaccination to elicit CD8 T cells, in vivo study of CD8 T cell development, and construction of multivalent MHC/peptide reagents for the enumeration and tracking of T cells - particularly when the antigenic peptide has relatively weak affinity for the MHC.

Original languageEnglish (US)
Pages (from-to)6280-6289
Number of pages10
JournalJournal of Immunology
Volume178
Issue number10
DOIs
StatePublished - May 15 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Disulfide bond engineering to trap peptides in the MHC class I binding groove'. Together they form a unique fingerprint.

  • Cite this

    Truscott, S. M., Lybarger, L., Martinko, J. M., Mitaksov, V. E., Kranz, D. M., Connolly, J. M., Fremont, D. H., & Hansen, T. H. (2007). Disulfide bond engineering to trap peptides in the MHC class I binding groove. Journal of Immunology, 178(10), 6280-6289. https://doi.org/10.4049/jimmunol.178.10.6280