Interaction of streptavidin-based peptide-MHC oligomers (tetramers) with cell-surface TCRs

Jennifer D. Stone, Maxim N. Artyomov, Adam S. Chervin, Arup K. Chakraborty, Herman N. Eisen, David M. Kranz

Research output: Contribution to journalArticle

Abstract

The binding of oligomeric peptide-MHC (pMHC) complexes to cell surface TCR can be considered to approximate TCR-pMHCinteractions at cell-cell interfaces. In this study, we analyzed the equilibrium binding of streptavidin-based pMHC oligomers(tetramers) and their dissociation kinetics from CD8 pos T cells from 2C-TCR transgenic mice and from T cell hybridomas thatexpressed the 2C TCR or a high-affinity mutant (m33) of this TCR. Our results show that the tetramers did not come close tosaturating cell-surface TCR (binding only 10-30% of cell-surface receptors), as is generally assumed in deriving affinity values(K D), in part because of dissociative losses from tetramer-stained cells. Guided by a kinetic model, the oligomer dissociation rateand equilibrium constants were seen to depend not only on monovalent association and dissociation rates (k off and k on), but also ona multivalent association rate (μ) and TCR cell-surface density. Our results suggest that dissociation rates could account for therecently described surprisingly high frequency of tetramer-negative, functionally competent T cells in some T cell responses.

Original languageEnglish (US)
Pages (from-to)6281-6290
Number of pages10
JournalJournal of Immunology
Volume187
Issue number12
DOIs
StatePublished - Dec 15 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Stone, J. D., Artyomov, M. N., Chervin, A. S., Chakraborty, A. K., Eisen, H. N., & Kranz, D. M. (2011). Interaction of streptavidin-based peptide-MHC oligomers (tetramers) with cell-surface TCRs. Journal of Immunology, 187(12), 6281-6290. https://doi.org/10.4049/jimmunol.1101734