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 journalArticle

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

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T-Cell Antigen Receptor
Major Histocompatibility Complex
Peptides
Adaptive Immunity
Libraries
Yeasts

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Adams, J. J., Narayanan, S., Liu, B., Birnbaum, M. E., Kruse, A. C., Bowerman, N. A., ... Garcia, K. C. (2011). T cell receptor signaling is limited by docking geometry to peptide-major histocompatibility complex. Immunity, 35(5), 681-693. https://doi.org/10.1016/j.immuni.2011.09.013

T cell receptor signaling is limited by docking geometry to peptide-major histocompatibility complex. / Adams, Jarrett J.; Narayanan, Samanthi; Liu, Baoyu; Birnbaum, Michael E.; Kruse, Andrew C.; Bowerman, Natalie A.; Chen, Wei; Levin, Aron M.; Connolly, Janet M.; Zhu, Cheng; Kranz, David M; Garcia, K. Christopher.

In: Immunity, Vol. 35, No. 5, 23.11.2011, p. 681-693.

Research output: Contribution to journalArticle

Adams, JJ, Narayanan, S, Liu, B, Birnbaum, ME, Kruse, AC, Bowerman, NA, Chen, W, Levin, AM, Connolly, JM, Zhu, C, Kranz, DM & Garcia, KC 2011, 'T cell receptor signaling is limited by docking geometry to peptide-major histocompatibility complex', Immunity, vol. 35, no. 5, pp. 681-693. https://doi.org/10.1016/j.immuni.2011.09.013
Adams JJ, Narayanan S, Liu B, Birnbaum ME, Kruse AC, Bowerman NA et al. T cell receptor signaling is limited by docking geometry to peptide-major histocompatibility complex. Immunity. 2011 Nov 23;35(5):681-693. https://doi.org/10.1016/j.immuni.2011.09.013
Adams, Jarrett J. ; Narayanan, Samanthi ; Liu, Baoyu ; Birnbaum, Michael E. ; Kruse, Andrew C. ; Bowerman, Natalie A. ; Chen, Wei ; Levin, Aron M. ; Connolly, Janet M. ; Zhu, Cheng ; Kranz, David M ; Garcia, K. Christopher. / T cell receptor signaling is limited by docking geometry to peptide-major histocompatibility complex. In: Immunity. 2011 ; Vol. 35, No. 5. pp. 681-693.
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