@article{13b8fa2de9ac4086aaf2859b18752e53,
title = "Initiation of signal transduction through the T cell receptor requires the peptide multivalent engagement of MHC ligands",
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.",
author = "Boniface, {J. Jay} and Rabinowitz, {Joshua D.} and Christoph W{\"u}lfing and Johannes Hampl and Ziv Reich and Altman, {John D.} and Kantor, {Ronald M.} and Craig Beeson and McConnell, {Harden M.} and Davis, {Mark M.}",
note = "Funding Information: We thank Loan Nguyen, Suzanne Erickson-Ybarra, Sharmila Sudanagunta, Dan Lyons, Brian Trenchak, and Kristin Baldwin for their help in the preparation of IE k and 2B4, Korey Singleton for early dimer studies, Ashley Chi for RT-PCR help, Paul Allen for PL17, Cathy Carswell-Crumpton for cell sorting assistance, Susan Palmieri and Mike Sjaastad for help with calcium imaging, Max Krummel for discussions, and Peter Shatz for early supplies of the BirA enzyme. J. J. B. was supported by a National Institutes of Health training grant and by a fellowship from the Irvington Institute for Medical Research, J. D. R. by the Medical Scientist Training Program, C. W. by a European Molecular Biology Organization long-term fellowship and the Howard Hughes Medical Institute, C. B. by a fellowship from the Cancer Research Institute, and J. D. A. by a fellowship from the American Cancer Society. This work was supported by grants from the National Institutes of Health (H. M. M. and M. M. D.) and the Howard Hughes Medical Institute (M. M. D.).",
year = "1998",
month = oct,
doi = "10.1016/S1074-7613(00)80629-9",
language = "English (US)",
volume = "9",
pages = "459--466",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "4",
}