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PDBsum entry 2fyy
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Immune system
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PDB id
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2fyy
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References listed in PDB file
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Key reference
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Title
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Tcr alpha genes direct mhc restriction in the potent human t cell response to a class i-Bound viral epitope.
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Authors
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J.J.Miles,
N.A.Borg,
R.M.Brennan,
F.E.Tynan,
L.Kjer-Nielsen,
S.L.Silins,
M.J.Bell,
J.M.Burrows,
J.Mccluskey,
J.Rossjohn,
S.R.Burrows.
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Ref.
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J Immunol, 2006,
177,
6804-6814.
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PubMed id
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Abstract
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The underlying generic properties of alphabeta TCRs that control MHC restriction
remain largely unresolved. To investigate MHC restriction, we have examined the
CTL response to a viral epitope that binds promiscuously to two human leukocyte
Ags (HLAs) that differ by a single amino acid at position 156. Individuals
expressing either HLA-B*3501 (156Leucine) or HLA-B*3508 (156Arginine) showed a
potent CTL response to the 407HPVGEADYFEY417 epitope from EBV. Interestingly,
the response was characterized by highly restricted TCR beta-chain usage in both
HLA-B*3501+ and HLA-B*3508+ individuals; however, this conserved TRBV9+
beta-chain was associated with distinct TCR alpha-chains depending upon the
HLA-B*35 allele expressed by the virus-exposed host. Functional assays confirmed
that TCR alpha-chain usage determined the HLA restriction of the CTLs.
Structural studies revealed significant differences in the mobility of the
peptide when bound to HLA-B*3501 or HLA-B*3508. In HLA-B*3501, the bulged
section of the peptide was disordered, whereas in HLA-B*3508 the bulged epitope
adopted an ordered conformation. Collectively, these data demonstrate not only
that mobile MHC-bound peptides can be highly immunogenic but can also stimulate
an extremely biased TCR repertoire. In addition, TCR alpha-chain usage is shown
to play a critical role in controlling MHC restriction between closely related
allomorphs.
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