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PDBsum entry 2ak4
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Immune system
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PDB id
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2ak4
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Contents |
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276 a.a.
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99 a.a.
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13 a.a.
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204 a.a.
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241 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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T cell receptor recognition of a 'Super-Bulged' Major histocompatibility complex class i-Bound peptide.
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Authors
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F.E.Tynan,
S.R.Burrows,
A.M.Buckle,
C.S.Clements,
N.A.Borg,
J.J.Miles,
T.Beddoe,
J.C.Whisstock,
M.C.Wilce,
S.L.Silins,
J.M.Burrows,
L.Kjer-Nielsen,
L.Kostenko,
A.W.Purcell,
J.Mccluskey,
J.Rossjohn.
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Ref.
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Nat Immunol, 2005,
6,
1114-1122.
[DOI no: ]
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PubMed id
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Abstract
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Unusually long major histocompatibility complex (MHC) class I-restricted
epitopes are important in immunity, but their 'bulged' conformation represents a
potential obstacle to alphabeta T cell receptor (TCR)-MHC class I docking. To
elucidate how such recognition is achieved while still preserving MHC
restriction, we have determined here the structure of a TCR in complex with
HLA-B(*)3508 presenting a peptide 13 amino acids in length. This complex was
atypical of TCR-peptide-MHC class I interactions, being dominated at the
interface by peptide-mediated interactions. The TCR assumed two distinct
orientations, swiveling on top of the centrally bulged, rigid peptide such that
only limited contacts were made with MHC class I. Although the TCR-peptide
recognition resembled an antibody-antigen interaction, the TCR-MHC class I
contacts defined a minimal 'generic footprint' of MHC-restriction. Thus our
findings simultaneously demonstrate the considerable adaptability of the TCR and
the 'shape' of MHC restriction.
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Figure 2.
Figure 2. SB27 TCR contacts at the interface. (a) 'Footprint'
of the SB27 TCR on the HLA-B^*3508-LPEP complex. There are
limited MHC-mediated contacts with the SB27 TCR on the gray
surface representation of the HLA-B^*3508 heavy chain. (b)
'Footprint' of the LC13 TCR in complex with HLA-B8-FLRGRAYGL,
showing the focus toward the carboxy-terminal end of the
peptide^5. (c) Closer view of the SB27 TCR contacts with the
HLA-B^*3508-LPEP complex. HLA-B^*3508  -helices,
light gray; peptide, orange; conformation of Gln155 as it
appears in the binary complex (HLA-B^*3508-LPEP)3, dark gray;
side chains from the triad of residues mediating
MHC-restriction, gold. CDR loop colors are as in Figure 1b.
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Figure 4.
Figure 4. SB27 TCR recognition of the HLA-B^*3508-LPEP complex
is antibody like and is dominated by TCR-peptide interactions.
(a,b) GRASP image of the SB27 TCR-peptide interaction (a)
compared with that of a complex between an Fab and a peptide
from human rhinovirus viral capsid protein VP2 (b; Protein Data
Bank accession number, 1A3R)46. TCR V[  ]and
Fab V[H], red; TCR V  and
Fab V[L], blue; Epstein-Barr virus LPEP and rhinovirus VP2
peptides, yellow. (c) Closer view of the SB27 TCR interactions
with the solvent-exposed side chains of the LPEP peptide.
Peptide, orange; CDR loop colors are as in Figure 1b. (d)
Dose-response assays of analogs of the 13-residue peptide
(LPEPLPQGQLTAY) that include single-amino acid substitutions,
assessing recognition by SB27 CTLs (chromium-release assays,
left) and binding to 'empty' HLA-B^*3508 with the transporter
associated with antigen processing-deficient T2-B^*3508 (right).
Peptides recognized well in the cytotoxicity assays are assumed
to bind well to HLA-B^*3508 and are therefore excluded from the
MHC-binding assays (NT). Data represent peptide concentrations
for half-maximal lysis or binding calculated from dose-response
curves for each peptide and are representative of two
independent experiments with similar results.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Immunol
(2005,
6,
1114-1122)
copyright 2005.
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