Cutting edge: A role for inside-out signaling in TCR regulation of CD28 ligand binding

Mariano Sanchez-Lockhart, Minsoo Kim, Jim Miller

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Efficient T cell activation depends on the engagement of both TCR and CD28, although the molecular mechanisms that control this signal integration are not fully understood. Using fluorescence resonance energy transfer, we show that T cell activation can drive a reorientation of the cytosolic tails of the CD28 dimer. However, this is not mediated through CD28 ligand binding. Rather, TCR signaling itself mediates this conformation change in CD28. We also show that TCR signaling can induce CD28-ligand interactions. Although the CD28 dimer appears to bind ligand monovalently in solution, we show that both ligand binding sites are required to efficiently recruit CD28 to the immunological synapse. These results suggest, that analogous to the cross-talk from TCR that regulates integrin activation, TCR-initiated inside-out signaling may induce a conformational change to the extracellular domains of CD28, enabling ligand binding and initiating CD28 signaling.

Original languageEnglish (US)
Pages (from-to)5515-5519
Number of pages5
JournalJournal of Immunology
Issue number11
StatePublished - Dec 1 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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