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PDBsum entry 4qrp
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Immune system
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PDB id
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4qrp
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Contents |
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276 a.a.
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99 a.a.
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203 a.a.
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243 a.a.
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PDB id:
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| Name: |
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Immune system
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Title:
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Crystal structure of hla b 0801 In complex with hskkkcdel and dd31 tcr
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Structure:
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Hla class i histocompatibility antigen, b-8 alpha chain. Chain: a, f. Synonym: mhc class i antigen b 8. Engineered: yes. Beta-2-microglobulin. Chain: b, g. Synonym: beta-2-microglobulin form pi 5.3. Engineered: yes. Ns3-4a protein.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: hla-b, hlab. Expressed in: escherichia coli. Expression_system_taxid: 469008. Gene: b2m, cdabp0092, hdcma22p. Synthetic: yes. Hepatitis c virus.
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Resolution:
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2.90Å
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R-factor:
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0.209
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R-free:
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0.248
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Authors:
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S.Gras,R.Berry,I.S.Lucet,J.Rossjohn
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Key ref:
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U.K.Nivarthi
et al.
(2014).
An extensive antigenic footprint underpins immunodominant TCR adaptability against a hypervariable viral determinant.
J Immunol,
193,
5402-5413.
PubMed id:
DOI:
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Date:
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02-Jul-14
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Release date:
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12-Nov-14
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PROCHECK
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Headers
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References
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P01889
(1B07_HUMAN) -
HLA class I histocompatibility antigen, B alpha chain from Homo sapiens
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Seq:
Struc:
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362 a.a.
276 a.a.*
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P61769
(B2MG_HUMAN) -
Beta-2-microglobulin from Homo sapiens
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Seq:
Struc:
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119 a.a.
99 a.a.
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DOI no:
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J Immunol
193:5402-5413
(2014)
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PubMed id:
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An extensive antigenic footprint underpins immunodominant TCR adaptability against a hypervariable viral determinant.
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U.K.Nivarthi,
S.Gras,
L.Kjer-Nielsen,
R.Berry,
I.S.Lucet,
J.J.Miles,
S.L.Tracy,
A.W.Purcell,
D.S.Bowden,
M.Hellard,
J.Rossjohn,
J.McCluskey,
M.Bharadwaj.
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ABSTRACT
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Mutations in T cell epitopes are implicated in hepatitis C virus (HCV)
persistence and can impinge on vaccine development. We recently demonstrated a
narrow bias in the human TCR repertoire targeted at an immunodominant, but
highly mutable, HLA-B*0801-restricted epitope ((1395)HSKKKCDEL(1403) [HSK]). To
investigate if the narrow TCR repertoire facilitates CTL escape, structural and
biophysical studies were undertaken, alongside comprehensive functional analysis
of T cells targeted at the natural variants of HLA-B*0801-HSK in different HCV
genotypes and quasispecies. Interestingly, within the TCR-HLA-B*0801-HSK
complex, the TCR contacts all available surface-exposed residues of the HSK
determinant. This broad epitope coverage facilitates cross-genotypic reactivity
and recognition of common mutations reported in HCV quasispecies, albeit to a
varying degree. Certain mutations did abrogate T cell reactivity; however,
natural variants comprising these mutations are reportedly rare and transient in
nature, presumably due to fitness costs. Overall, despite a narrow bias, the TCR
accommodated frequent mutations by acting like a blanket over the hypervariable
epitope, thereby providing effective viral immunity. Our findings simultaneously
advance the understanding of anti-HCV immunity and indicate the potential for
cross-genotype HCV vaccines.
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