Reversed T cell receptor docking on a major histocompatibility class I complex limits involvement in the immune response

Stephanie Gras, Jesseka Chadderton, Claudia M. Del Campo, Carine Farenc, Florian Wiede, Tracy M. Josephs, Xavier Y.X. Sng, Michiko Mirams, Katherine A. Watson, Tony Tiganis, Kylie M. Quinn, Jamie Rossjohn, Nicole L. La Gruta

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The anti-viral T cell response is drawn from the naive T cell repertoire. During influenza infection, the CD8+ T cell response to an H-2Db-restricted nucleoprotein epitope (NP366) is characterized by preferential expansion of T cells bearing TRBV13+ T cell receptors (TCRs) and avoidance of TRBV17+ T cells, despite the latter dominating the naive precursor repertoire. We found two TRBV17+ TCRs that bound H-2Db-NP366 with a 180° reversed polarity compared to the canonical TCR-pMHC-I docking. The TRBV17 β-chain dominated the interaction and, whereas the complementarity determining region-3 (CDR3) loops exclusively mediated contacts with the MHC-I, peptide specificity was attributable to germline-encoded recognition. Nevertheless, the TRBV17+ TCR exhibited moderate affinity toward H-2Db-NP366 and was capable of signal transduction. Thus, the naive CD8+ T cell pool can comprise TCRs adopting reversed pMHC-I docking modes that limit their involvement in the immune response.
Original languageEnglish
Pages (from-to)749-760
Number of pages12
JournalImmunity
Volume45
Issue number4
DOIs
Publication statusPublished - 18 Oct 2016

Keywords

  • reversed TCR docking
  • T cell activation
  • T cell recruitment
  • TCR recognition of pMHCI

Cite this

@article{83151b24802b41409e8b997c054dc670,
title = "Reversed T cell receptor docking on a major histocompatibility class I complex limits involvement in the immune response",
abstract = "The anti-viral T cell response is drawn from the naive T cell repertoire. During influenza infection, the CD8+ T cell response to an H-2Db-restricted nucleoprotein epitope (NP366) is characterized by preferential expansion of T cells bearing TRBV13+ T cell receptors (TCRs) and avoidance of TRBV17+ T cells, despite the latter dominating the naive precursor repertoire. We found two TRBV17+ TCRs that bound H-2Db-NP366 with a 180° reversed polarity compared to the canonical TCR-pMHC-I docking. The TRBV17 β-chain dominated the interaction and, whereas the complementarity determining region-3 (CDR3) loops exclusively mediated contacts with the MHC-I, peptide specificity was attributable to germline-encoded recognition. Nevertheless, the TRBV17+ TCR exhibited moderate affinity toward H-2Db-NP366 and was capable of signal transduction. Thus, the naive CD8+ T cell pool can comprise TCRs adopting reversed pMHC-I docking modes that limit their involvement in the immune response.",
keywords = "reversed TCR docking, T cell activation, T cell recruitment, TCR recognition of pMHCI",
author = "Stephanie Gras and Jesseka Chadderton and {Del Campo}, {Claudia M.} and Carine Farenc and Florian Wiede and Josephs, {Tracy M.} and Sng, {Xavier Y.X.} and Michiko Mirams and Watson, {Katherine A.} and Tony Tiganis and Quinn, {Kylie M.} and Jamie Rossjohn and {La Gruta}, {Nicole L.}",
year = "2016",
month = "10",
day = "18",
doi = "10.1016/j.immuni.2016.09.007",
language = "English",
volume = "45",
pages = "749--760",
journal = "Immunity",
issn = "1074-7613",
publisher = "Elsevier",
number = "4",

}

Reversed T cell receptor docking on a major histocompatibility class I complex limits involvement in the immune response. / Gras, Stephanie; Chadderton, Jesseka; Del Campo, Claudia M.; Farenc, Carine; Wiede, Florian; Josephs, Tracy M.; Sng, Xavier Y.X.; Mirams, Michiko; Watson, Katherine A.; Tiganis, Tony; Quinn, Kylie M.; Rossjohn, Jamie; La Gruta, Nicole L.

In: Immunity, Vol. 45, No. 4, 18.10.2016, p. 749-760.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Reversed T cell receptor docking on a major histocompatibility class I complex limits involvement in the immune response

AU - Gras, Stephanie

AU - Chadderton, Jesseka

AU - Del Campo, Claudia M.

AU - Farenc, Carine

AU - Wiede, Florian

AU - Josephs, Tracy M.

AU - Sng, Xavier Y.X.

AU - Mirams, Michiko

AU - Watson, Katherine A.

AU - Tiganis, Tony

AU - Quinn, Kylie M.

AU - Rossjohn, Jamie

AU - La Gruta, Nicole L.

PY - 2016/10/18

Y1 - 2016/10/18

N2 - The anti-viral T cell response is drawn from the naive T cell repertoire. During influenza infection, the CD8+ T cell response to an H-2Db-restricted nucleoprotein epitope (NP366) is characterized by preferential expansion of T cells bearing TRBV13+ T cell receptors (TCRs) and avoidance of TRBV17+ T cells, despite the latter dominating the naive precursor repertoire. We found two TRBV17+ TCRs that bound H-2Db-NP366 with a 180° reversed polarity compared to the canonical TCR-pMHC-I docking. The TRBV17 β-chain dominated the interaction and, whereas the complementarity determining region-3 (CDR3) loops exclusively mediated contacts with the MHC-I, peptide specificity was attributable to germline-encoded recognition. Nevertheless, the TRBV17+ TCR exhibited moderate affinity toward H-2Db-NP366 and was capable of signal transduction. Thus, the naive CD8+ T cell pool can comprise TCRs adopting reversed pMHC-I docking modes that limit their involvement in the immune response.

AB - The anti-viral T cell response is drawn from the naive T cell repertoire. During influenza infection, the CD8+ T cell response to an H-2Db-restricted nucleoprotein epitope (NP366) is characterized by preferential expansion of T cells bearing TRBV13+ T cell receptors (TCRs) and avoidance of TRBV17+ T cells, despite the latter dominating the naive precursor repertoire. We found two TRBV17+ TCRs that bound H-2Db-NP366 with a 180° reversed polarity compared to the canonical TCR-pMHC-I docking. The TRBV17 β-chain dominated the interaction and, whereas the complementarity determining region-3 (CDR3) loops exclusively mediated contacts with the MHC-I, peptide specificity was attributable to germline-encoded recognition. Nevertheless, the TRBV17+ TCR exhibited moderate affinity toward H-2Db-NP366 and was capable of signal transduction. Thus, the naive CD8+ T cell pool can comprise TCRs adopting reversed pMHC-I docking modes that limit their involvement in the immune response.

KW - reversed TCR docking

KW - T cell activation

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