Initiation of signal transduction through the T cell receptor requires the peptide multivalent engagement of MHC ligands

J. Jay Boniface, Joshua D. Rabinowitz, Christoph Wülfing, Johannes Hampl, Ziv Reich, John D. Altman, Ronald M. Kantor, Craig Beeson, Harden M. McConnell, Mark M. Davis

Research output: Contribution to journalArticle

303 Scopus citations

Abstract

While much is known about intracellular signaling events in T cells when T cell receptors (TCRs) are engaged, the mechanism by which signaling is initiated is unclear. We have constructed defined oligomers of soluble antigen-major histocompatibility complex (MHC) molecules, the natural ligands for the TCR. Using these to stimulate specific T cells in vitro, we find that agonist peptide/MHC ligands are nonstimulatory as monomers and minimally stimulatory as dimers. Similarly, a partial-agonist ligand is very weakly active as a tetramer. In contrast, trimeric or tetrameric agonist ligands that engage multiple TCRs for a sustained duration are potent stimuli. Ligand-driven formation of TCR clusters seems required for effective activation and helps to explain the specificity and sensitivity of T cells.

Original languageEnglish (US)
Pages (from-to)459-466
Number of pages8
JournalImmunity
Volume9
Issue number4
DOIs
StatePublished - Oct 1998
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Boniface, J. J., Rabinowitz, J. D., Wülfing, C., Hampl, J., Reich, Z., Altman, J. D., Kantor, R. M., Beeson, C., McConnell, H. M., & Davis, M. M. (1998). Initiation of signal transduction through the T cell receptor requires the peptide multivalent engagement of MHC ligands. Immunity, 9(4), 459-466. https://doi.org/10.1016/S1074-7613(00)80629-9