Structural interplay between germline interactions and adaptive recognition determines the bandwidth of TCR-peptide-MHC cross-reactivity

Jarrett J. Adams, Samanthi Narayanan, Michael E. Birnbaum, Sachdev S. Sidhu, Sydney J. Blevins, Marvin H. Gee, Leah V. Sibener, Brian M. Baker, David M Kranz, K. Christopher Garcia

Research output: Contribution to journalArticle

Abstract

The T cell antigen receptor (TCR)-peptide-major histocompatibility complex (MHC) interface is composed of conserved and diverse regions, yet the relative contribution of each in shaping recognition by T cells remains unclear. Here we isolated cross-reactive peptides with limited homology, which allowed us to compare the structural properties of nine peptides for a single TCR-MHC pair. The TCR's cross-reactivity was rooted in highly similar recognition of an apical 'hot-spot' position in the peptide with tolerance of sequence variation at ancillary positions. Furthermore, we found a striking structural convergence onto a germline-mediated interaction between the TCR CDR1α region and the MHC α2 helix in twelve TCR-peptide-MHC complexes. Our studies suggest that TCR-MHC germline-mediated constraints, together with a focus on a small peptide hot spot, might place limits on peptide antigen cross-reactivity.

Original languageEnglish (US)
Pages (from-to)87-94
Number of pages8
JournalNature Immunology
Volume17
Issue number1
DOIs
StatePublished - Jan 1 2016

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T-Cell Antigen Receptor
Major Histocompatibility Complex
Peptides
T-Lymphocytes
Antigens

ASJC Scopus subject areas

  • Immunology

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Adams, J. J., Narayanan, S., Birnbaum, M. E., Sidhu, S. S., Blevins, S. J., Gee, M. H., ... Garcia, K. C. (2016). Structural interplay between germline interactions and adaptive recognition determines the bandwidth of TCR-peptide-MHC cross-reactivity. Nature Immunology, 17(1), 87-94. https://doi.org/10.1038/ni.3310

Structural interplay between germline interactions and adaptive recognition determines the bandwidth of TCR-peptide-MHC cross-reactivity. / Adams, Jarrett J.; Narayanan, Samanthi; Birnbaum, Michael E.; Sidhu, Sachdev S.; Blevins, Sydney J.; Gee, Marvin H.; Sibener, Leah V.; Baker, Brian M.; Kranz, David M; Garcia, K. Christopher.

In: Nature Immunology, Vol. 17, No. 1, 01.01.2016, p. 87-94.

Research output: Contribution to journalArticle

Adams, JJ, Narayanan, S, Birnbaum, ME, Sidhu, SS, Blevins, SJ, Gee, MH, Sibener, LV, Baker, BM, Kranz, DM & Garcia, KC 2016, 'Structural interplay between germline interactions and adaptive recognition determines the bandwidth of TCR-peptide-MHC cross-reactivity', Nature Immunology, vol. 17, no. 1, pp. 87-94. https://doi.org/10.1038/ni.3310
Adams, Jarrett J. ; Narayanan, Samanthi ; Birnbaum, Michael E. ; Sidhu, Sachdev S. ; Blevins, Sydney J. ; Gee, Marvin H. ; Sibener, Leah V. ; Baker, Brian M. ; Kranz, David M ; Garcia, K. Christopher. / Structural interplay between germline interactions and adaptive recognition determines the bandwidth of TCR-peptide-MHC cross-reactivity. In: Nature Immunology. 2016 ; Vol. 17, No. 1. pp. 87-94.
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