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PDBsum entry 5t6y
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Immune system
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PDB id
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5t6y
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References listed in PDB file
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Key reference
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Title
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Mhc-I peptides get out of the groove and enable a novel mechanism of HIV-1 escape.
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Authors
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P.Pymm,
P.T.Illing,
S.H.Ramarathinam,
G.M.O'Connor,
V.A.Hughes,
C.Hitchen,
D.A.Price,
B.K.Ho,
D.W.Mcvicar,
A.G.Brooks,
A.W.Purcell,
J.Rossjohn,
J.P.Vivian.
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Ref.
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Nat Struct Biol, 2017,
24,
387-394.
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PubMed id
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Abstract
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Major histocompatibility complex class I (MHC-I) molecules play a crucial role
in immunity by capturing peptides for presentation to T cells and natural killer
(NK) cells. The peptide termini are tethered within the MHC-I antigen-binding
groove, but it is unknown whether other presentation modes occur. Here we show
that 20% of the HLA-B*57:01 peptide repertoire comprises N-terminally extended
sets characterized by a common motif at position 1 (P1) to P2. Structures of
HLA-B*57:01 presenting N-terminally extended peptides, including the
immunodominant HIV-1 Gag epitope TW10 (TSTLQEQIGW), showed that the N terminus
protrudes from the peptide-binding groove. The common escape mutant TSNLQEQIGW
bound HLA-B*57:01 canonically, adopting a dramatically different conformation
than the TW10 peptide. This affected recognition by killer cell
immunoglobulin-like receptor (KIR) 3DL1 expressed on NK cells. We thus define a
previously uncharacterized feature of the human leukocyte antigen class I
(HLA-I) immunopeptidome that has implications for viral immune escape. We
further suggest that recognition of the HLA-B*57:01-TW10 epitope is governed by
a 'molecular tension' between the adaptive and innate immune systems.
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