2FYY

The role of T cell receptor alpha genes in directing human MHC restriction

2FYY の概要

• エントリーDOI: 10.2210/pdb2fyy/pdb
• 関連するPDBエントリー: 2fz3
• 分子名称: HLA class I histocompatibility antigen, B-35 alpha chain, Beta-2-microglobulin, 11-mer peptide from Epstein-Barr nuclear antigen 1, ... (4 entities in total)
• 機能のキーワード: mhc, hla-b*3501, ig domain, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 45015.78

構造登録者

Miles, J.J.,Borg, N.A. (登録日: 2006-02-08, 公開日: 2006-12-26, 最終更新日: 2024-10-09)

主引用文献

Miles, J.J.,Borg, N.A.,Brennan, R.M.,Tynan, F.E.,Kjer-Nielsen, L.,Silins, S.L.,Bell, M.J.,Burrows, J.M.,McCluskey, J.,Rossjohn, J.,Burrows, S.R.
TCR alpha genes direct MHC restriction in the potent human T cell response to a class I-bound viral epitope.
J Immunol., 177:6804-6814, 2006

PubMed Abstract: 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.

PubMed: 17082594
DOI: 10.4049/jimmunol.177.10.6804

実験手法

X-RAY DIFFRACTION (1.5 Å)