The Stimulatory Potency of T Cell Antigens Is Influenced by the Formation of the Immunological Synapse

Sašo Čemerski, Jayajit Das, Jason Locasale, Phoebe Arnold, Emanuele Giurisato, Mary A A. Markiewicz, Daved Fremont, Paul M. Allen, Arup K. Chakraborty, Andrey S. Shaw

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

T cell activation is predicated on the interaction between the T cell receptor and peptide-major histocompatibility (pMHC) ligands. The factors that determine the stimulatory potency of a pMHC molecule remain unclear. We describe results showing that a peptide exhibiting many hallmarks of a weak agonist stimulates T cells to proliferate more than the wild-type agonist ligand. An in silico approach suggested that the inability to form the central supramolecular activation cluster (cSMAC) could underlie the increased proliferation. This conclusion was supported by experiments that showed that enhancing cSMAC formation reduced stimulatory capacity of the weak peptide. Our studies highlight the fact that a complex interplay of factors determines the quality of a T cell antigen.

Original languageEnglish
Pages (from-to)345-355
Number of pages11
JournalImmunity
Volume26
Issue number3
DOIs
StatePublished - Mar 23 2007

Keywords

  • CELLIMMUNO
  • MOLIMMUNO
  • SIGNALING

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