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PDBsum entry 3hg1
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Immune system
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PDB id
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3hg1
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Contents |
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276 a.a.
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100 a.a.
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194 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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Germ line-Governed recognition of a cancer epitope by an immunodominant human t-Cell receptor.
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Authors
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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.
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Ref.
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J Biol Chem, 2009,
284,
27281-27289.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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.
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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.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2009,
284,
27281-27289)
copyright 2009.
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