1zsd

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(New page: 200px<br /> <applet load="1zsd" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zsd, resolution 1.700&Aring;" /> '''Crystal Structure ...)
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caption="1zsd, resolution 1.700&Aring;" />
caption="1zsd, resolution 1.700&Aring;" />
'''Crystal Structure Of HLA-B*3501 Presenting an 11-Mer EBV Antigen EPLPQGQLTAY'''<br />
'''Crystal Structure Of HLA-B*3501 Presenting an 11-Mer EBV Antigen EPLPQGQLTAY'''<br />
==Overview==
==Overview==
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MHC class I molecules generally present peptides of 8-10 aa long, forming, an extended coil in the HLA cleft. Although longer peptides can also bind, to class I molecules, they tend to bulge from the cleft and it is not, known whether the TCR repertoire has sufficient plasticity to recognize, these determinants during the antiviral CTL response. In this study, we, show that unrelated individuals infected with EBV generate a significant, CTL response directed toward an HLA-B*3501-restricted, 11-mer epitope from, the BZLF1 Ag. The 11-mer determinant adopts a highly bulged conformation, with seven of the peptide side chains being solvent-exposed and available, for TCR interaction. Such a complex potentially creates a structural, challenge for TCR corecognition of both HLA-B*3501 and the peptide Ag., Surprisingly, unrelated B*3501 donors recognizing the 11-mer use identical, or closely related alphabeta TCR sequences that share particular CDR3, motifs. Within the small number of dominant CTL clonotypes observed, each, has discrete fine specificity for the exposed side chain residues of the, peptide. The data show that bulged viral peptides are indeed immunogenic, but suggest that the highly constrained TCR repertoire reflects a limit to, TCR diversity when responding to some unusual MHC peptide ligands.
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MHC class I molecules generally present peptides of 8-10 aa long, forming an extended coil in the HLA cleft. Although longer peptides can also bind to class I molecules, they tend to bulge from the cleft and it is not known whether the TCR repertoire has sufficient plasticity to recognize these determinants during the antiviral CTL response. In this study, we show that unrelated individuals infected with EBV generate a significant CTL response directed toward an HLA-B*3501-restricted, 11-mer epitope from the BZLF1 Ag. The 11-mer determinant adopts a highly bulged conformation with seven of the peptide side chains being solvent-exposed and available for TCR interaction. Such a complex potentially creates a structural challenge for TCR corecognition of both HLA-B*3501 and the peptide Ag. Surprisingly, unrelated B*3501 donors recognizing the 11-mer use identical or closely related alphabeta TCR sequences that share particular CDR3 motifs. Within the small number of dominant CTL clonotypes observed, each has discrete fine specificity for the exposed side chain residues of the peptide. The data show that bulged viral peptides are indeed immunogenic but suggest that the highly constrained TCR repertoire reflects a limit to TCR diversity when responding to some unusual MHC peptide ligands.
==Disease==
==Disease==
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==About this Structure==
==About this Structure==
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1ZSD is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1ZSD OCA].
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1ZSD is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZSD OCA].
==Reference==
==Reference==
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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: Burrows, J.M.]]
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[[Category: Burrows, J M.]]
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[[Category: Burrows, S.R.]]
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[[Category: Burrows, S R.]]
[[Category: Elhassen, D.]]
[[Category: Elhassen, D.]]
[[Category: Kjer-Nielsen, L.]]
[[Category: Kjer-Nielsen, L.]]
[[Category: McCluskey, J.]]
[[Category: McCluskey, J.]]
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[[Category: Miles, J.J.]]
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[[Category: Miles, J J.]]
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[[Category: Purcell, A.W.]]
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[[Category: Purcell, A W.]]
[[Category: Rossjohn, J.]]
[[Category: Rossjohn, J.]]
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[[Category: Silins, S.L.]]
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[[Category: Silins, S L.]]
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[[Category: Tynan, F.E.]]
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[[Category: Tynan, F E.]]
[[Category: b*3501]]
[[Category: b*3501]]
[[Category: b35]]
[[Category: b35]]
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[[Category: major histocompatibility complex i]]
[[Category: major histocompatibility complex i]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:40:26 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:18:42 2008''

Revision as of 14:18, 21 February 2008


1zsd, resolution 1.700Å

Drag the structure with the mouse to rotate

Crystal Structure Of HLA-B*3501 Presenting an 11-Mer EBV Antigen EPLPQGQLTAY

Contents

Overview

MHC class I molecules generally present peptides of 8-10 aa long, forming an extended coil in the HLA cleft. Although longer peptides can also bind to class I molecules, they tend to bulge from the cleft and it is not known whether the TCR repertoire has sufficient plasticity to recognize these determinants during the antiviral CTL response. In this study, we show that unrelated individuals infected with EBV generate a significant CTL response directed toward an HLA-B*3501-restricted, 11-mer epitope from the BZLF1 Ag. The 11-mer determinant adopts a highly bulged conformation with seven of the peptide side chains being solvent-exposed and available for TCR interaction. Such a complex potentially creates a structural challenge for TCR corecognition of both HLA-B*3501 and the peptide Ag. Surprisingly, unrelated B*3501 donors recognizing the 11-mer use identical or closely related alphabeta TCR sequences that share particular CDR3 motifs. Within the small number of dominant CTL clonotypes observed, each has discrete fine specificity for the exposed side chain residues of the peptide. The data show that bulged viral peptides are indeed immunogenic but suggest that the highly constrained TCR repertoire reflects a limit to TCR diversity when responding to some unusual MHC peptide ligands.

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

1ZSD is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

CTL recognition of a bulged viral peptide involves biased TCR selection., Miles JJ, Elhassen D, Borg NA, Silins SL, Tynan FE, Burrows JM, Purcell AW, Kjer-Nielsen L, Rossjohn J, Burrows SR, McCluskey J, J Immunol. 2005 Sep 15;175(6):3826-34. PMID:16148129

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