2fz3

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spinqualitylabelsall models 2fz3, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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.

Disease

Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[142830], Hypoproteinemia, hypercatabolic OMIM:[109700], Spondyloarthropathy, susceptibility to, 1 OMIM:[142830], Stevens-Johnson syndrome, carbamazepine-induced, susceptibility to OMIM:[142830]

About this Structure

2FZ3 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

TCR alpha genes direct MHC restriction in the potent human T cell response to a class I-bound viral epitope., Miles JJ, Borg NA, Brennan RM, Tynan FE, Kjer-Nielsen L, Silins SL, Bell MJ, Burrows JM, McCluskey J, Rossjohn J, Burrows SR, J Immunol. 2006 Nov 15;177(10):6804-14. PMID:17082594

Page seeded by OCA on Fri Feb 15 17:26:56 2008