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PDBsum entry 2fyy
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protein ligands Protein-protein interface(s) links
Immune system PDB id
2fyy

 

 

 

 

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Contents
Protein chains
276 a.a. *
99 a.a. *
Ligands
HIS-PRO-VAL-GLY
PHE-GLU-TYR
Waters ×295
* Residue conservation analysis
PDB id:
2fyy
Name: Immune system
Title: The role of t cell receptor alpha genes in directing human mhc restriction
Structure: Hla class i histocompatibility antigen, b-35 alpha chain. Chain: a. Synonym: hla-b 3501 Heavy chain, mhc class i antigen b 35. Engineered: yes. Beta-2-microglobulin. Chain: b. Synonym: b2m. Engineered: yes. 11-mer peptide from epstein-barr nuclear antigen 1.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Synthetic: yes. Other_details: synthetic peptide
Resolution:
1.50Å     R-factor:   0.225     R-free:   0.236
Authors: J.J.Miles,N.A.Borg
Key ref: J.J.Miles et al. (2006). TCR alpha genes direct MHC restriction in the potent human T cell response to a class I-bound viral epitope. J Immunol, 177, 6804-6814. PubMed id: 17082594
Date:
08-Feb-06     Release date:   26-Dec-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
O19626  (O19626_HUMAN) -  HLA-B35 (Fragment) from Homo sapiens
Seq:
Struc: 		322 a.a.
276 a.a.
Protein chain
Pfam   ArchSchema ?
P61769  (B2MG_HUMAN) -  Beta-2-microglobulin from Homo sapiens
Seq:
Struc: 		119 a.a.
99 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
J Immunol 177:6804-6814 (2006)
PubMed id: 17082594  
 
 
TCR alpha genes direct MHC restriction in the potent human T cell response to a class I-bound viral epitope.
J.J.Miles, N.A.Borg, R.M.Brennan, F.E.Tynan, L.Kjer-Nielsen, S.L.Silins, M.J.Bell, J.M.Burrows, J.McCluskey, J.Rossjohn, S.R.Burrows.
 
  ABSTRACT  
 
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.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21301479 J.J.Miles, D.C.Douek, and D.A.Price (2011).
Bias in the αβ T-cell repertoire: implications for disease pathogenesis and vaccination.
  Immunol Cell Biol, 89, 375-387.  
21301478 S.Gras, L.Kjer-Nielsen, Z.Chen, J.Rossjohn, and J.McCluskey (2011).
The structural bases of direct T-cell allorecognition: implications for T-cell-mediated transplant rejection.
  Immunol Cell Biol, 89, 388-395.  
21301481 S.R.Burrows, D.J.Moss, and R.Khanna (2011).
Understanding human T-cell-mediated immunoregulation through herpesviruses.
  Immunol Cell Biol, 89, 352-358.  
20212169 A.Theodossis, C.Guillonneau, A.Welland, L.K.Ely, C.S.Clements, N.A.Williamson, A.I.Webb, J.A.Wilce, R.J.Mulder, M.A.Dunstone, P.C.Doherty, J.McCluskey, A.W.Purcell, S.J.Turner, and J.Rossjohn (2010).
Constraints within major histocompatibility complex class I restricted peptides: presentation and consequences for T-cell recognition.
  Proc Natl Acad Sci U S A, 107, 5534-5539.
PDB codes: 3l3d 3l3g 3l3h 3l3i 3l3j 3l3k
20976198 I.K.Macdonald, M.Harkiolaki, L.Hunt, T.Connelley, A.V.Carroll, N.D.MacHugh, S.P.Graham, E.Y.Jones, W.I.Morrison, D.R.Flower, and S.A.Ellis (2010).
MHC class I bound to an immunodominant Theileria parva epitope demonstrates unconventional presentation to T cell receptors.
  PLoS Pathog, 6, e1001149.
PDB code: 2xfx
20616031 S.Gras, L.Kedzierski, S.A.Valkenburg, K.Laurie, Y.C.Liu, J.T.Denholm, M.J.Richards, G.F.Rimmelzwaan, A.Kelso, P.C.Doherty, S.J.Turner, J.Rossjohn, and K.Kedzierska (2010).
Cross-reactive CD8+ T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses.
  Proc Natl Acad Sci U S A, 107, 12599-12604.
PDB codes: 3lkn 3lko 3lkp 3lkq 3lkr 3lks
20566715 S.Gras, Z.Chen, J.J.Miles, Y.C.Liu, M.J.Bell, L.C.Sullivan, L.Kjer-Nielsen, R.M.Brennan, J.M.Burrows, M.A.Neller, R.Khanna, A.W.Purcell, A.G.Brooks, J.McCluskey, J.Rossjohn, and S.R.Burrows (2010).
Allelic polymorphism in the T cell receptor and its impact on immune responses.
  J Exp Med, 207, 1555-1567.
PDB codes: 3mv7 3mv8 3mv9
20483993 S.R.Burrows, Z.Chen, J.K.Archbold, F.E.Tynan, T.Beddoe, L.Kjer-Nielsen, J.J.Miles, R.Khanna, D.J.Moss, Y.C.Liu, S.Gras, L.Kostenko, R.M.Brennan, C.S.Clements, A.G.Brooks, A.W.Purcell, J.McCluskey, and J.Rossjohn (2010).
Hard wiring of T cell receptor specificity for the major histocompatibility complex is underpinned by TCR adaptability.
  Proc Natl Acad Sci U S A, 107, 10608-10613.
PDB codes: 3kww 3kxf
18342005 D.I.Godfrey, J.Rossjohn, and J.McCluskey (2008).
The fidelity, occasional promiscuity, and versatility of T cell receptor recognition.
  Immunity, 28, 304-314.  
18809922 L.Derré, M.Bruyninx, P.Baumgaertner, M.Ferber, D.Schmid, A.Leimgruber, V.Zoete, P.Romero, O.Michielin, D.E.Speiser, and N.Rufer (2008).
Distinct sets of alphabeta TCRs confer similar recognition of tumor antigen NY-ESO-1157-165 by interacting with its central Met/Trp residues.
  Proc Natl Acad Sci U S A, 105, 15010-15015.  
18207719 S.Gras, L.Kjer-Nielsen, S.R.Burrows, J.McCluskey, and J.Rossjohn (2008).
T-cell receptor bias and immunity.
  Curr Opin Immunol, 20, 119-125.  
18301425 V.Venturi, D.A.Price, D.C.Douek, and M.P.Davenport (2008).
The molecular basis for public T-cell responses?
  Nat Rev Immunol, 8, 231-238.  
17259989 F.E.Tynan, H.H.Reid, L.Kjer-Nielsen, J.J.Miles, M.C.Wilce, L.Kostenko, N.A.Borg, N.A.Williamson, T.Beddoe, A.W.Purcell, S.R.Burrows, J.McCluskey, and J.Rossjohn (2007).
A T cell receptor flattens a bulged antigenic peptide presented by a major histocompatibility complex class I molecule.
  Nat Immunol, 8, 268-276.
PDB codes: 2nw2 2nw3 2nx5
17357107 J.M.Burrows, K.K.Wynn, F.E.Tynan, J.Archbold, J.J.Miles, M.J.Bell, R.M.Brennan, S.Walker, J.McCluskey, J.Rossjohn, R.Khanna, and S.R.Burrows (2007).
The impact of HLA-B micropolymorphism outside primary peptide anchor pockets on the CTL response to CMV.
  Eur J Immunol, 37, 946-953.  
17459926 R.M.Brennan, J.J.Miles, S.L.Silins, M.J.Bell, J.M.Burrows, and S.R.Burrows (2007).
Predictable alphabeta T-cell receptor selection toward an HLA-B*3501-restricted human cytomegalovirus epitope.
  J Virol, 81, 7269-7273.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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