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PDBsum entry 3o4l
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Immune system
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PDB id
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3o4l
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Contents |
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276 a.a.
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100 a.a.
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195 a.a.
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245 a.a.
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References listed in PDB file
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Key reference
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Title
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Genetic and structural basis for selection of a ubiquitous t cell receptor deployed in epstein-Barr virus infection.
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Authors
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J.J.Miles,
A.M.Bulek,
D.K.Cole,
E.Gostick,
A.J.Schauenburg,
G.Dolton,
V.Venturi,
M.P.Davenport,
M.P.Tan,
S.R.Burrows,
L.Wooldridge,
D.A.Price,
P.J.Rizkallah,
A.K.Sewell.
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Ref.
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Plos Pathog, 2010,
6,
e1001198.
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PubMed id
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Abstract
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Despite the ∼10(18) αβ T cell receptor (TCR) structures that can be randomly
manufactured by the human thymus, some surface more frequently than others. The
pinnacles of this distortion are public TCRs, which exhibit amino acid-identical
structures across different individuals. Public TCRs are thought to result from
both recombinatorial bias and antigen-driven selection, but the mechanisms that
underlie inter-individual TCR sharing are still largely theoretical. To examine
this phenomenon at the atomic level, we solved the co-complex structure of one
of the most widespread and numerically frequent public TCRs in the human
population. The archetypal AS01 public TCR recognizes an immunodominant BMLF1
peptide, derived from the ubiquitous Epstein-Barr virus, bound to HLA-A*0201.
The AS01 TCR was observed to dock in a diagonal fashion, grasping the solvent
exposed peptide crest with two sets of complementarity-determining region (CDR)
loops, and was fastened to the peptide and HLA-A*0201 platform with residue sets
found only within TCR genes biased in the public response. Computer simulations
of a random V(D)J recombination process demonstrated that both TCRα and TCRβ
amino acid sequences could be manufactured easily, thereby explaining the
prevalence of this receptor across different individuals. Interestingly, the
AS01 TCR was encoded largely by germline DNA, indicating that the TCR loci
already comprise gene segments that specifically recognize this ancient
pathogen. Such pattern recognition receptor-like traits within the αβ TCR
system further blur the boundaries between the adaptive and innate immune
systems.
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