2FZ3

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

Summary for 2FZ3

• Entry DOI: 10.2210/pdb2fz3/pdb
• Related: 2FYY
• Descriptor: 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)
• Functional Keywords: mhc, hla-b*3508, ig domain, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 45059.82

Authors

Miles, J.J.,Borg, N.A. (deposition date: 2006-02-09, release date: 2006-12-26, Last modification date: 2024-10-23)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.9 Å)