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| {{STRUCTURE_2fz3| PDB=2fz3 | SCENE= }} | | {{STRUCTURE_2fz3| PDB=2fz3 | SCENE= }} |
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| '''The role of T cell receptor alpha genes in directing human MHC restriction'''
| | ===The role of T cell receptor alpha genes in directing human MHC restriction=== |
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| ==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. | | The line below this paragraph, {{ABSTRACT_PUBMED_17082594}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 17082594 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_17082594}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Ig domain]] | | [[Category: Ig domain]] |
| [[Category: Mhc]] | | [[Category: Mhc]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 04:28:32 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 04:46:16 2008'' |
