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PDBsum entry 4pj8
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Immune system
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PDB id
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4pj8
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Contents |
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260 a.a.
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97 a.a.
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197 a.a.
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244 a.a.
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References listed in PDB file
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Key reference
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Title
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A molecular basis underpinning the t cell receptor heterogeneity of mucosal-Associated invariant t cells.
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Authors
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S.B.Eckle,
R.W.Birkinshaw,
L.Kostenko,
A.J.Corbett,
H.E.Mcwilliam,
R.Reantragoon,
Z.Chen,
N.A.Gherardin,
T.Beddoe,
L.Liu,
O.Patel,
B.Meehan,
D.P.Fairlie,
J.A.Villadangos,
D.I.Godfrey,
L.Kjer-Nielsen,
J.Mccluskey,
J.Rossjohn.
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Ref.
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J Exp Med, 2014,
211,
1585-1600.
[DOI no: ]
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PubMed id
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Abstract
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Mucosal-associated invariant T (MAIT) cells express an invariant T cell receptor
(TCR) α-chain (TRAV1-2 joined to TRAJ33, TRAJ20, or TRAJ12 in humans), which
pairs with an array of TCR β-chains. MAIT TCRs can bind folate- and
riboflavin-based metabolites restricted by the major histocompatibility complex
(MHC)-related class I-like molecule, MR1. However, the impact of MAIT TCR and
MR1-ligand heterogeneity on MAIT cell biology is unclear. We show how a
previously uncharacterized MR1 ligand, acetyl-6-formylpterin (Ac-6-FP), markedly
stabilized MR1, potently up-regulated MR1 cell surface expression, and inhibited
MAIT cell activation. These enhanced properties of Ac-6-FP were attributable to
structural alterations in MR1 that subsequently affected MAIT TCR recognition
via conformational changes within the complementarity-determining region (CDR)
3β loop. Analysis of seven TRBV6-1(+) MAIT TCRs demonstrated how CDR3β
hypervariability impacted on MAIT TCR recognition by altering TCR flexibility
and contacts with MR1 and the Ag itself. Ternary structures of TRBV6-1, TRBV6-4,
and TRBV20(+) MAIT TCRs in complex with MR1 bound to a potent riboflavin-based
antigen (Ag) showed how variations in TRBV gene usage exclusively impacted on
MR1 contacts within a consensus MAIT TCR-MR1 footprint. Moreover, differential
TRAJ gene usage was readily accommodated within a conserved MAIT TCR-MR1-Ag
docking mode. Collectively, MAIT TCR heterogeneity can fine-tune MR1 recognition
in an Ag-dependent manner, thereby modulating MAIT cell recognition.
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