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2fz3

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(New page: 200px<br /> <applet load="2fz3" size="450" color="white" frame="true" align="right" spinBox="true" caption="2fz3, resolution 1.90&Aring;" /> '''The role of T cell ...)
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[[Image:2fz3.gif|left|200px]]<br />
 
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<applet load="2fz3" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2fz3, resolution 1.90&Aring;" />
 
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'''The role of T cell receptor alpha genes in directing human MHC restriction'''<br />
 
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==Overview==
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==The role of T cell receptor alpha genes in directing human MHC restriction==
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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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<StructureSection load='2fz3' size='340' side='right'caption='[[2fz3]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2fz3]] 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=2FZ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FZ3 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2fz3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fz3 OCA], [https://pdbe.org/2fz3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fz3 RCSB], [https://www.ebi.ac.uk/pdbsum/2fz3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fz3 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/O19626_HUMAN O19626_HUMAN]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fz/2fz3_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2fz3 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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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==Disease==
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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>
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Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142830 142830]], Hypoproteinemia, hypercatabolic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=109700 109700]], Spondyloarthropathy, susceptibility to, 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142830 142830]], Stevens-Johnson syndrome, carbamazepine-induced, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142830 142830]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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2FZ3 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=2FZ3 OCA].
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</div>
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<div class="pdbe-citations 2fz3" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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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://ispc.weizmann.ac.il//pmbin/getpm?pmid=17082594 17082594]
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*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]]
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*[[MHC 3D structures|MHC 3D structures]]
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*[[MHC I 3D structures|MHC I 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Human herpesvirus 4 strain B95-8]]
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[[Category: Borg, N.A.]]
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[[Category: Large Structures]]
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[[Category: Miles, J.J.]]
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[[Category: Borg NA]]
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[[Category: hla-b*3508]]
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[[Category: Miles JJ]]
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[[Category: ig domain]]
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[[Category: mhc]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:12:15 2007''
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The role of T cell receptor alpha genes in directing human MHC restriction

PDB ID 2fz3

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