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[[Image:2fyy.jpg|left|200px]]


{{Structure
==The role of T cell receptor alpha genes in directing human MHC restriction==
|PDB= 2fyy |SIZE=350|CAPTION= <scene name='initialview01'>2fyy</scene>, resolution 1.50&Aring;
<StructureSection load='2fyy' size='340' side='right'caption='[[2fyy]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND=  
<table><tr><td colspan='2'>[[2fyy]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_herpesvirus_4_strain_B95-8 Human herpesvirus 4 strain B95-8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FYY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FYY FirstGlance]. <br>
|ACTIVITY=  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5&#8491;</td></tr>
|GENE=  
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2fyy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fyy OCA], [https://pdbe.org/2fyy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fyy RCSB], [https://www.ebi.ac.uk/pdbsum/2fyy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fyy ProSAT]</span></td></tr>
|DOMAIN=
</table>
|RELATEDENTRY=[[2fz3|2FZ3]]
== Function ==
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2fyy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fyy OCA], [http://www.ebi.ac.uk/pdbsum/2fyy PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2fyy RCSB]</span>
[https://www.uniprot.org/uniprot/O19626_HUMAN O19626_HUMAN]
}}
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fy/2fyy_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2fyy ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.


'''The role of T cell receptor alpha genes in directing human MHC restriction'''
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<ref>PMID:17082594</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2fyy" style="background-color:#fffaf0;"></div>


==Overview==
==See Also==
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.
*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]]
 
*[[MHC 3D structures|MHC 3D structures]]
==About this Structure==
*[[MHC I 3D structures|MHC I 3D structures]]
2FYY is a [[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=2FYY OCA].
== References ==
 
<references/>
==Reference==
__TOC__
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:[http://www.ncbi.nlm.nih.gov/pubmed/17082594 17082594]
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Human herpesvirus 4 strain B95-8]]
[[Category: Borg, N A.]]
[[Category: Large Structures]]
[[Category: Miles, J J.]]
[[Category: Borg NA]]
[[Category: hla-b*3501]]
[[Category: Miles JJ]]
[[Category: ig domain]]
[[Category: mhc]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:09:34 2008''

Latest revision as of 07:37, 9 October 2024

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

2fyy, resolution 1.50Å

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