2fz3

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==Overview==
==Overview==
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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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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==
==Disease==
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Protein complex]]
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[[Category: Borg, N.A.]]
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[[Category: Borg, N A.]]
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[[Category: Miles, J.J.]]
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[[Category: Miles, J J.]]
[[Category: hla-b*3508]]
[[Category: hla-b*3508]]
[[Category: ig domain]]
[[Category: ig domain]]
[[Category: mhc]]
[[Category: mhc]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:26:56 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:26:34 2008''

Revision as of 15:26, 21 February 2008

Image:2fz3.jpg

2fz3, resolution 1.90Å

Drag the structure with the mouse to rotate

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

Contents

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

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