Diversity of T cells restricted by the MHC class I-related molecule MR1 facilitates differential antigen recognition

Nicholas A. Gherardin, Andrew N. Keller, Rachel E. Woolley, Jerome Le Nours, David S. Ritchie, Paul J. Neeson, Richard W. Birkinshaw, Sidonia B.G. Eckle, John N. Waddington, Ligong Liu, David P. Fairlie, Adam P. Uldrich, Daniel G. Pellicci, James McCluskey, Dale I. Godfrey, Jamie Rossjohn

Research output: Contribution to journalArticleResearchpeer-review

Abstract

A characteristic of mucosal-associated invariant T (MAIT) cells is the expression of TRAV1-2+ T cell receptors (TCRs) that are activated by riboflavin metabolite-based antigens (Ag) presented by the MHC-I related molecule, MR1. Whether the MR1-restricted T cell repertoire and associated Ag responsiveness extends beyond these cells remains unclear. Here, we describe MR1 autoreactivity and folate-derivative reactivity in a discrete subset of TRAV1-2+ MAIT cells. This recognition was attributable to CDR3β loop-mediated effects within a consensus TRAV1-2+ TCR-MR1-Ag footprint. Furthermore, we have demonstrated differential folate- and riboflavin-derivative reactivity by a diverse population of “atypical” TRAV1-2 MR1-restricted T cells. We have shown that TRAV1-2 T cells are phenotypically heterogeneous and largely distinct from TRAV1-2+ MAIT cells. A TRAV1-2 TCR docks more centrally on MR1, thereby adopting a markedly different molecular footprint to the TRAV1-2+ TCR. Accordingly, diversity within the MR1-restricted T cell repertoire leads to differing MR1-restricted Ag specificity.
Original languageEnglish
Pages (from-to)32-45
Number of pages14
JournalImmunity
Volume44
Issue number1
DOIs
Publication statusPublished - 19 Jan 2016

Cite this

Gherardin, Nicholas A. ; Keller, Andrew N. ; Woolley, Rachel E. ; Le Nours, Jerome ; Ritchie, David S. ; Neeson, Paul J. ; Birkinshaw, Richard W. ; Eckle, Sidonia B.G. ; Waddington, John N. ; Liu, Ligong ; Fairlie, David P. ; Uldrich, Adam P. ; Pellicci, Daniel G. ; McCluskey, James ; Godfrey, Dale I. ; Rossjohn, Jamie. / Diversity of T cells restricted by the MHC class I-related molecule MR1 facilitates differential antigen recognition. In: Immunity. 2016 ; Vol. 44, No. 1. pp. 32-45.
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title = "Diversity of T cells restricted by the MHC class I-related molecule MR1 facilitates differential antigen recognition",
abstract = "A characteristic of mucosal-associated invariant T (MAIT) cells is the expression of TRAV1-2+ T cell receptors (TCRs) that are activated by riboflavin metabolite-based antigens (Ag) presented by the MHC-I related molecule, MR1. Whether the MR1-restricted T cell repertoire and associated Ag responsiveness extends beyond these cells remains unclear. Here, we describe MR1 autoreactivity and folate-derivative reactivity in a discrete subset of TRAV1-2+ MAIT cells. This recognition was attributable to CDR3β loop-mediated effects within a consensus TRAV1-2+ TCR-MR1-Ag footprint. Furthermore, we have demonstrated differential folate- and riboflavin-derivative reactivity by a diverse population of “atypical” TRAV1-2− MR1-restricted T cells. We have shown that TRAV1-2− T cells are phenotypically heterogeneous and largely distinct from TRAV1-2+ MAIT cells. A TRAV1-2− TCR docks more centrally on MR1, thereby adopting a markedly different molecular footprint to the TRAV1-2+ TCR. Accordingly, diversity within the MR1-restricted T cell repertoire leads to differing MR1-restricted Ag specificity.",
author = "Gherardin, {Nicholas A.} and Keller, {Andrew N.} and Woolley, {Rachel E.} and {Le Nours}, Jerome and Ritchie, {David S.} and Neeson, {Paul J.} and Birkinshaw, {Richard W.} and Eckle, {Sidonia B.G.} and Waddington, {John N.} and Ligong Liu and Fairlie, {David P.} and Uldrich, {Adam P.} and Pellicci, {Daniel G.} and James McCluskey and Godfrey, {Dale I.} and Jamie Rossjohn",
year = "2016",
month = "1",
day = "19",
doi = "10.1016/j.immuni.2015.12.005",
language = "English",
volume = "44",
pages = "32--45",
journal = "Immunity",
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Gherardin, NA, Keller, AN, Woolley, RE, Le Nours, J, Ritchie, DS, Neeson, PJ, Birkinshaw, RW, Eckle, SBG, Waddington, JN, Liu, L, Fairlie, DP, Uldrich, AP, Pellicci, DG, McCluskey, J, Godfrey, DI & Rossjohn, J 2016, 'Diversity of T cells restricted by the MHC class I-related molecule MR1 facilitates differential antigen recognition' Immunity, vol. 44, no. 1, pp. 32-45. https://doi.org/10.1016/j.immuni.2015.12.005

Diversity of T cells restricted by the MHC class I-related molecule MR1 facilitates differential antigen recognition. / Gherardin, Nicholas A.; Keller, Andrew N.; Woolley, Rachel E.; Le Nours, Jerome; Ritchie, David S.; Neeson, Paul J.; Birkinshaw, Richard W.; Eckle, Sidonia B.G.; Waddington, John N.; Liu, Ligong; Fairlie, David P.; Uldrich, Adam P.; Pellicci, Daniel G.; McCluskey, James; Godfrey, Dale I.; Rossjohn, Jamie.

In: Immunity, Vol. 44, No. 1, 19.01.2016, p. 32-45.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Diversity of T cells restricted by the MHC class I-related molecule MR1 facilitates differential antigen recognition

AU - Gherardin, Nicholas A.

AU - Keller, Andrew N.

AU - Woolley, Rachel E.

AU - Le Nours, Jerome

AU - Ritchie, David S.

AU - Neeson, Paul J.

AU - Birkinshaw, Richard W.

AU - Eckle, Sidonia B.G.

AU - Waddington, John N.

AU - Liu, Ligong

AU - Fairlie, David P.

AU - Uldrich, Adam P.

AU - Pellicci, Daniel G.

AU - McCluskey, James

AU - Godfrey, Dale I.

AU - Rossjohn, Jamie

PY - 2016/1/19

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N2 - A characteristic of mucosal-associated invariant T (MAIT) cells is the expression of TRAV1-2+ T cell receptors (TCRs) that are activated by riboflavin metabolite-based antigens (Ag) presented by the MHC-I related molecule, MR1. Whether the MR1-restricted T cell repertoire and associated Ag responsiveness extends beyond these cells remains unclear. Here, we describe MR1 autoreactivity and folate-derivative reactivity in a discrete subset of TRAV1-2+ MAIT cells. This recognition was attributable to CDR3β loop-mediated effects within a consensus TRAV1-2+ TCR-MR1-Ag footprint. Furthermore, we have demonstrated differential folate- and riboflavin-derivative reactivity by a diverse population of “atypical” TRAV1-2− MR1-restricted T cells. We have shown that TRAV1-2− T cells are phenotypically heterogeneous and largely distinct from TRAV1-2+ MAIT cells. A TRAV1-2− TCR docks more centrally on MR1, thereby adopting a markedly different molecular footprint to the TRAV1-2+ TCR. Accordingly, diversity within the MR1-restricted T cell repertoire leads to differing MR1-restricted Ag specificity.

AB - A characteristic of mucosal-associated invariant T (MAIT) cells is the expression of TRAV1-2+ T cell receptors (TCRs) that are activated by riboflavin metabolite-based antigens (Ag) presented by the MHC-I related molecule, MR1. Whether the MR1-restricted T cell repertoire and associated Ag responsiveness extends beyond these cells remains unclear. Here, we describe MR1 autoreactivity and folate-derivative reactivity in a discrete subset of TRAV1-2+ MAIT cells. This recognition was attributable to CDR3β loop-mediated effects within a consensus TRAV1-2+ TCR-MR1-Ag footprint. Furthermore, we have demonstrated differential folate- and riboflavin-derivative reactivity by a diverse population of “atypical” TRAV1-2− MR1-restricted T cells. We have shown that TRAV1-2− T cells are phenotypically heterogeneous and largely distinct from TRAV1-2+ MAIT cells. A TRAV1-2− TCR docks more centrally on MR1, thereby adopting a markedly different molecular footprint to the TRAV1-2+ TCR. Accordingly, diversity within the MR1-restricted T cell repertoire leads to differing MR1-restricted Ag specificity.

UR - http://www.ncbi.nlm.nih.gov/pubmed/26795251

U2 - 10.1016/j.immuni.2015.12.005

DO - 10.1016/j.immuni.2015.12.005

M3 - Article

VL - 44

SP - 32

EP - 45

JO - Immunity

JF - Immunity

SN - 1074-7613

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