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PDBsum entry 5vue
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Immune system
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PDB id
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5vue
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DOI no:
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Nat Commun
9:4693
(2018)
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PubMed id:
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HLA-B57 micropolymorphism defines the sequence and conformational breadth of the immunopeptidome.
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P.T.Illing,
P.Pymm,
N.P.Croft,
H.G.Hilton,
V.Jojic,
A.S.Han,
J.L.Mendoza,
N.A.Mifsud,
N.L.Dudek,
J.McCluskey,
P.Parham,
J.Rossjohn,
J.P.Vivian,
A.W.Purcell.
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ABSTRACT
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Immunophenotypic differences between closely related human leukocyte antigen
(HLA) alleles have been associated with divergent clinical outcomes in
infection, autoimmunity, transplantation and drug hypersensitivity. Here we
explore the impact of micropolymorphism on peptide antigen presentation by three
closely related HLA molecules, HLA-B*57:01, HLA-B*57:03 and HLA-B*58:01, that
are differentially associated with the HIV elite controller phenotype and
adverse drug reactions. For each allotype, we mine HLA ligand data sets derived
from the same parental cell proteome to define qualitative differences in
peptide presentation using classical peptide binding motifs and an unbiased
statistical approach. The peptide repertoires show marked qualitative overlap,
with 982 peptides presented by all allomorphs. However, differences in peptide
abundance, HLA-peptide stability, and HLA-bound conformation demonstrate that
HLA micropolymorphism impacts more than simply the range of peptide ligands.
These differences provide grounds for distinct immune reactivity and insights
into the capacity of micropolymorphism to diversify immune outcomes.
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');
}
}
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