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PDBsum entry 1rk0
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Immune system
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PDB id
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1rk0
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Contents |
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* Residue conservation analysis
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J Exp Med
200:1445-1454
(2004)
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PubMed id:
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Structural basis for the restoration of TCR recognition of an MHC allelic variant by peptide secondary anchor substitution.
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M.J.Miley,
I.Messaoudi,
B.M.Metzner,
Y.Wu,
J.Nikolich-Zugich,
D.H.Fremont.
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ABSTRACT
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Major histocompatibility complex (MHC) class I variants H-2K(b) and H-2K(bm8)
differ primarily in the B pocket of the peptide-binding groove, which serves to
sequester the P2 secondary anchor residue. This polymorphism determines
resistance to lethal herpes simplex virus (HSV-1) infection by modulating T cell
responses to the immunodominant glycoprotein B(498-505) epitope, HSV8. We
studied the molecular basis of these effects and confirmed that T cell receptors
raised against K(b)-HSV8 cannot recognize H-2K(bm8)-HSV8. However, substitution
of Ser(P2) to Glu(P2) (peptide H2E) reversed T cell receptor (TCR) recognition;
H-2K(bm8)-H2E was recognized whereas H-2K(b)-H2E was not. Insight into the
structural basis of this discrimination was obtained by determining the crystal
structures of all four MHC class I molecules in complex with bound peptide
(pMHCs). Surprisingly, we find no concerted pMHC surface differences that can
explain the differential TCR recognition. However, a correlation is apparent
between the recognition data and the underlying peptide-binding groove chemistry
of the B pocket, revealing that secondary anchor residues can profoundly affect
TCR engagement through mechanisms distinct from the alteration of the resting
state conformation of the pMHC surface.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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A.Ziegler,
C.A.Müller,
R.A.Böckmann,
and
B.Uchanska-Ziegler
(2009).
Low-affinity peptides and T-cell selection.
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Trends Immunol,
30,
53-60.
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G.J.Mizejewski
(2009).
Alpha-fetoprotein (AFP)-derived peptides as epitopes for hepatoma immunotherapy: a commentary.
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Cancer Immunol Immunother,
58,
159-170.
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J.K.Archbold,
W.A.Macdonald,
S.Gras,
L.K.Ely,
J.J.Miles,
M.J.Bell,
R.M.Brennan,
T.Beddoe,
M.C.Wilce,
C.S.Clements,
A.W.Purcell,
J.McCluskey,
S.R.Burrows,
and
J.Rossjohn
(2009).
Natural micropolymorphism in human leukocyte antigens provides a basis for genetic control of antigen recognition.
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J Exp Med,
206,
209-219.
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PDB codes:
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V.Mitaksov,
S.M.Truscott,
L.Lybarger,
J.M.Connolly,
T.H.Hansen,
and
D.H.Fremont
(2007).
Structural engineering of pMHC reagents for T cell vaccines and diagnostics.
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Chem Biol,
14,
909-922.
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PDB codes:
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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
codes are
shown on the right.
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Links
