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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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References listed in PDB file
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Key reference
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Title
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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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Authors
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M.J.Miley,
I.Messaoudi,
B.M.Metzner,
Y.Wu,
J.Nikolich-Zugich,
D.H.Fremont.
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Ref.
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J Exp Med, 2004,
200,
1445-1454.
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PubMed id
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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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