|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
276 a.a.
|
|
|
|
|
|
|
|
|
|
|
100 a.a.
|
|
|
|
|
|
|
|
|
|
|
194 a.a.
|
|
|
|
|
|
|
|
|
|
|
244 a.a.
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Immune system
|
|
|
Title:
|
|
Germline-governed recognition of a cancer epitope by an immunodominant human t cell receptor
|
|
Structure:
|
|
Mhc class i antigen. Chain: a. Fragment: residues 25-300. Synonym: mhc class i antigen a 2. Engineered: yes. Beta-2-microglobulin. Chain: b. Fragment: residues 21-119. Synonym: beta-2-microglobulin.
|
|
Source:
|
|
Homo sapiens. Human. Organism_taxid: 9606. Gene: hla-a, hlaa. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: b2m, cdabp0092, hdcma22p. Synthetic: yes. Organism_taxid: 9606
|
|
Resolution:
|
|
|
3.00Å
|
R-factor:
|
0.229
|
R-free:
|
0.304
|
|
|
Authors:
|
|
D.K.Cole,F.Yuan,P.J.Rizkallah,J.J.Miles,E.Gostick,D.A.Price,G.F.Gao, B.K.Jakobsen,A.K.Sewell
|
Key ref:
|
|
D.K.Cole
et al.
(2009).
Germ line-governed recognition of a cancer epitope by an immunodominant human T-cell receptor.
J Biol Chem,
284,
27281-27289.
PubMed id:
DOI:
|
|
|
Date:
|
|
|
13-May-09
|
Release date:
|
28-Jul-09
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
Q8WLS4
(Q8WLS4_HUMAN) -
MHC class I antigen (Fragment) from Homo sapiens
|
|
|
|
Seq:
Struc:
|
|
|
|
317 a.a.
276 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
P61769
(B2MG_HUMAN) -
Beta-2-microglobulin from Homo sapiens
|
|
|
|
Seq:
Struc:
|
|
|
|
119 a.a.
100 a.a.*
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
DOI no:
|
J Biol Chem
284:27281-27289
(2009)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Germ line-governed recognition of a cancer epitope by an immunodominant human T-cell receptor.
|
|
D.K.Cole,
F.Yuan,
P.J.Rizkallah,
J.J.Miles,
E.Gostick,
D.A.Price,
G.F.Gao,
B.K.Jakobsen,
A.K.Sewell.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
CD8(+) T-cells specific for MART-1-(26-35), a dominant melanoma epitope
restricted by human leukocyte antigen (HLA)-A*0201, are exceptionally common in
the naive T-cell repertoire. Remarkably, the TRAV12-2 gene is used to encode the
T-cell receptor alpha (TCRalpha) chain in >87% of these T-cells. Here, the
molecular basis for this genetic bias is revealed from the structural and
thermodynamic properties of an archetypal TRAV12-2-encoded TCR complexed to the
clinically relevant heteroclitic peptide, ELAGIGILTV, bound to HLA-A*0201
(A2-ELA). Unusually, the TRAV12-2 germ line-encoded regions of the TCR dominate
the major atomic contacts with the peptide at the TCR/A2-ELA interface. This
"innate" pattern of antigen recognition probably explains the unique
characteristics and extraordinary frequencies of CD8(+) T-cell responses to this
epitope.
|
|
|
|
|
|
| |
Selected figure(s)
|
|
|
|
| |
|
|
|
|
|
|
Figure 1.
A, the co-crystal structure of MEL5 (α chain shown as a
yellow schematic diagram, β chain shown as a salmon schematic
diagram) bound to the HLA-A*0201 (shown as green and blue
schematic diagrams) molecule complexed with the ELAGIGILTV
peptide (shown as blue sticks). B, expanded view of the
interface between the MEL5 variable domain bound to the A2-ELA
surface (colors as in A). The overall conformation of the
ELAGIGILTV peptide (N to C terminus, left to right), including
the central peptide bulge, is displayed. C, view from above of
the MEL5 CDR loops bound to the A2-ELA surface (colors as in A;
MEL5 CDR loops shown as spheres). The MEL5 TCR binds toward the
N terminus of the peptide, making contacts with the peptide via
its CDR1 and CDR3 loops and contacts with the MHC surface via
its CDR1 and CDR2 loops.
|
|
Figure 2.
A, the interactions between the CDR loops of MEL5 α chain
(shown as yellow sticks) and the ELAGIGILTV peptide (shown as
blue sticks). Electrostatic interactions are depicted as black
dotted lines, and vdW interactions are shown as red dotted
lines. B, the interactions between the CDR loops of MEL5 β
chain (shown as salmon sticks) and the ELAGIGILTV peptide (shown
as blue sticks). Electrostatic interactions are depicted as
black dotted lines, and vdW interactions are shown as red dotted
lines.
|
|
|
|
|
|
| |
The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2009,
284,
27281-27289)
copyright 2009.
|
|
| |
Figures were
selected
by an automated process.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
A.K.Sewell
(2012).
Why must T cells be cross-reactive?
|
| |
Nat Rev Immunol,
12,
669-677.
|
|
|
|
|
|
|
D.H.Aggen,
A.S.Chervin,
F.K.Insaidoo,
K.H.Piepenbrink,
B.M.Baker,
and
D.M.Kranz
(2011).
Identification and engineering of human variable regions that allow expression of stable single-chain T cell receptors.
|
| |
Protein Eng Des Sel,
24,
361-372.
|
|
|
|
|
|
|
E.M.Iancu,
P.Baumgaertner,
S.Wieckowski,
D.E.Speiser,
and
N.Rufer
(2011).
Profile of a serial killer: cellular and molecular approaches to study individual cytotoxic T-cells following therapeutic vaccination.
|
| |
J Biomed Biotechnol,
2011,
452606.
|
|
|
|
|
|
|
J.J.Miles,
D.C.Douek,
and
D.A.Price
(2011).
Bias in the αβ T-cell repertoire: implications for disease pathogenesis and vaccination.
|
| |
Immunol Cell Biol,
89,
375-387.
|
|
|
|
|
|
|
K.M.Miles,
J.J.Miles,
F.Madura,
A.K.Sewell,
and
D.K.Cole
(2011).
Real time detection of peptide-MHC dissociation reveals that improvement of primary MHC-binding residues can have a minimal, or no, effect on stability.
|
| |
Mol Immunol,
48,
728-732.
|
|
|
|
|
|
|
D.K.Cole,
E.S.Edwards,
K.K.Wynn,
M.Clement,
J.J.Miles,
K.Ladell,
J.Ekeruche,
E.Gostick,
K.J.Adams,
A.Skowera,
M.Peakman,
L.Wooldridge,
D.A.Price,
and
A.K.Sewell
(2010).
Modification of MHC anchor residues generates heteroclitic peptides that alter TCR binding and T cell recognition.
|
| |
J Immunol,
185,
2600-2610.
|
|
|
|
|
|
|
J.J.Miles,
A.M.Bulek,
D.K.Cole,
E.Gostick,
A.J.Schauenburg,
G.Dolton,
V.Venturi,
M.P.Davenport,
M.P.Tan,
S.R.Burrows,
L.Wooldridge,
D.A.Price,
P.J.Rizkallah,
and
A.K.Sewell
(2010).
Genetic and structural basis for selection of a ubiquitous T cell receptor deployed in Epstein-Barr virus infection.
|
| |
PLoS Pathog,
6,
e1001198.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
O.Y.Borbulevych,
K.H.Piepenbrink,
B.E.Gloor,
D.R.Scott,
R.F.Sommese,
D.K.Cole,
A.K.Sewell,
and
B.M.Baker
(2009).
T cell receptor cross-reactivity directed by antigen-dependent tuning of peptide-MHC molecular flexibility.
|
| |
Immunity,
31,
885-896.
|
|
|
PDB codes:
|
|
|
|
|
|
|
The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
|
| |
Links
