T cell receptor signaling is limited by docking geometry to peptide-major histocompatibility complex

Jarrett J. Adams, Samanthi Narayanan, Baoyu Liu, Michael E. Birnbaum, Andrew C. Kruse, Natalie A. Bowerman, Wei Chen, Aron M. Levin, Janet M. Connolly, Cheng Zhu, David M. Kranz, K. Christopher Garcia

Research output: Contribution to journalArticlepeer-review

Abstract

T cell receptor (TCR) engagement of peptide-major histocompatibility complex (pMHC) is essential to adaptive immunity, but it is unknown whether TCR signaling responses are influenced by the binding topology of the TCR-peptide-MHC complex. We developed yeast-displayed pMHC libraries that enabled us to identify new peptide sequences reactive with a single TCR. Structural analysis showed that four peptides bound to the TCR with distinct 3D and 2D affinities using entirely different binding chemistries. Three of the peptides that shared a common docking mode, where key TCR-MHC germline interactions are preserved, induced TCR signaling. The fourth peptide failed to induce signaling and was recognized in a substantially different TCR-MHC binding mode that apparently exceeded geometric tolerances compatible with signaling. We suggest that the stereotypical TCR-MHC docking paradigm evolved from productive signaling geometries and that TCR signaling can be modulated by peptides that are recognized in alternative TCR-pMHC binding orientations.

Original languageEnglish (US)
Pages (from-to)681-693
Number of pages13
JournalImmunity
Volume35
Issue number5
DOIs
StatePublished - Nov 23 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'T cell receptor signaling is limited by docking geometry to peptide-major histocompatibility complex'. Together they form a unique fingerprint.

Cite this