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PDBsum entry 2vlr
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Immune system PDB id
2vlr

 

 

 

 

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Contents
Protein chains
276 a.a. *
100 a.a. *
199 a.a. *
240 a.a. *
Ligands
GLY-ILE-LEU-GLY-
PHE-VAL-PHE-THR-
LEU ×2
Waters ×583
* Residue conservation analysis
PDB id:
2vlr
Name: Immune system
Title: The structural dynamics and energetics of an immunodominant t-cell receptor are programmed by its vbeta domain
Structure: Hla class i histocompatibility antigen, a-2 alpha chain. Chain: a, f. Fragment: hla-a2, residues 25-300. Synonym: mhc class i antigen a 2. Engineered: yes. Beta-2-microglobulin. Chain: b, g. Engineered: yes. Flu matrix peptide.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Unidentified influenza virus. Organism_taxid: 11309. Expression_system_taxid: 562
Resolution:
2.30Å     R-factor:   0.222     R-free:   0.281
Authors: J.Ishizuka,G.Stewart-Jones,A.Van Der Merwe,J.Bell,A.Mcmichael,Y.Jones
Key ref: J.Ishizuka et al. (2008). The structural dynamics and energetics of an immunodominant T cell receptor are programmed by its Vbeta domain. Immunity, 28, 171-182. PubMed id: 18275829
Date:
15-Jan-08     Release date:   22-Jan-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P04439  (1A03_HUMAN) -  HLA class I histocompatibility antigen, A alpha chain from Homo sapiens
Seq:
Struc: 		365 a.a.
276 a.a.*
Protein chains
Pfam   ArchSchema ?
P61769  (B2MG_HUMAN) -  Beta-2-microglobulin from Homo sapiens
Seq:
Struc: 		119 a.a.
100 a.a.*
Protein chains
No UniProt id for this chain
Struc: 199 a.a.
Protein chains
No UniProt id for this chain
Struc: 240 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 21 residue positions (black crosses)

 

 
Immunity 28:171-182 (2008)
PubMed id: 18275829  
 
 
The structural dynamics and energetics of an immunodominant T cell receptor are programmed by its Vbeta domain.
J.Ishizuka, G.B.Stewart-Jones, A.van der Merwe, J.I.Bell, A.J.McMichael, E.Y.Jones.
 
  ABSTRACT  
 
Immunodominant and public T cell receptor (TCR) usage is relatively common in many viral diseases yet surprising in the context of the large naive TCR repertoire. We examined the highly conserved Vbeta17:Valpha10.2 JM22 T cell response to the influenza matrix peptide (58-66)-HLA-A*0201 (HLA-A2-flu) through extensive kinetic, thermodynamic, and structural analyses. We found several conformational adjustments that accompany JM22-HLA-A2-flu binding and identified a binding "hotspot" within the Vbeta domain of the TCR. Within this hotspot, key germline-encoded CDR1 and CDR2 loop residues and a crucial but commonly coded residue in the hypervariable region of CDR3 provide the basis for the substantial bias in the selection of the germline-encoded Vbeta17 domain. The chances of having a substantial number of T cells in the naive repertoire that have HLA-A2-flu-specific Vbeta17 receptors may consequently be relatively high, thus explaining the immunodominant usage of this clonotype.
 

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.  
21364947 J.M.Khan, and S.Ranganathan (2011).
Understanding TR Binding to pMHC Complexes: How Does a TR Scan Many pMHC Complexes yet Preferentially Bind to One.
  PLoS One, 6, e17194.  
20089450 J.D.Ahlers, and I.M.Belyakov (2010).
Lessons learned from natural infection: focusing on the design of protective T cell vaccines for HIV/AIDS.
  Trends Immunol, 31, 120-130.  
21124993 J.J.Miles, A.M.Bulek, D.K.Cole, E.Gostick, A.J.Schauenburg, G.Dolton, V.Venturi, M.P.Davenport, M.P.Tan, S.R.Burrows, L.Wooldridge, D.A.Price, P.J.Rizkallah, and A.K.Sewell (2010).
Genetic and structural basis for selection of a ubiquitous T cell receptor deployed in Epstein-Barr virus infection.
  PLoS Pathog, 6, e1001198.
PDB code: 3o4l
20333301 M.A.Patarroyo, A.Bermúdez, C.López, G.Yepes, and M.E.Patarroyo (2010).
3D analysis of the TCR/pMHCII complex formation in monkeys vaccinated with the first peptide inducing sterilizing immunity against human malaria.
  PLoS One, 5, e9771.  
20017116 R.L.Rich, and D.G.Myszka (2010).
Grading the commercial optical biosensor literature-Class of 2008: 'The Mighty Binders'.
  J Mol Recognit, 23, 1.  
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
19592275 D.G.Pellicci, O.Patel, L.Kjer-Nielsen, S.S.Pang, L.C.Sullivan, K.Kyparissoudis, A.G.Brooks, H.H.Reid, S.Gras, I.S.Lucet, R.Koh, M.J.Smyth, T.Mallevaey, J.L.Matsuda, L.Gapin, J.McCluskey, D.I.Godfrey, and J.Rossjohn (2009).
Differential recognition of CD1d-alpha-galactosyl ceramide by the V beta 8.2 and V beta 7 semi-invariant NKT T cell receptors.
  Immunity, 31, 47-59.
PDB codes: 3he6 3he7 3huj
19307587 G.Stewart-Jones, A.Wadle, A.Hombach, E.Shenderov, G.Held, E.Fischer, S.Kleber, F.Stenner-Liewen, S.Bauer, A.McMichael, A.Knuth, H.Abken, A.A.Hombach, V.Cerundolo, E.Y.Jones, and C.Renner (2009).
Rational development of high-affinity T-cell receptor-like antibodies.
  Proc Natl Acad Sci U S A, 106, 5784-5788.
PDB codes: 3gje 3gjf 3gjg 3hae
19125887 J.D.Stone, A.S.Chervin, and D.M.Kranz (2009).
T-cell receptor binding affinities and kinetics: impact on T-cell activity and specificity.
  Immunology, 126, 165-176.  
19734234 J.Ishizuka, K.Grebe, E.Shenderov, B.Peters, Q.Chen, Y.Peng, L.Wang, T.Dong, V.Pasquetto, C.Oseroff, J.Sidney, H.Hickman, V.Cerundolo, A.Sette, J.R.Bennink, A.McMichael, and J.W.Yewdell (2009).
Quantitating T cell cross-reactivity for unrelated peptide antigens.
  J Immunol, 183, 4337-4345.  
19139173 J.K.Archbold, W.A.Macdonald, S.Gras, L.K.Ely, J.J.Miles, M.J.Bell, R.M.Brennan, T.Beddoe, M.C.Wilce, C.S.Clements, A.W.Purcell, J.McCluskey, S.R.Burrows, and J.Rossjohn (2009).
Natural micropolymorphism in human leukocyte antigens provides a basis for genetic control of antigen recognition.
  J Exp Med, 206, 209-219.
PDB codes: 3dx6 3dx7 3dx8 3dx9 3dxa
18996721 J.P.Hodkinson, T.R.Jahn, S.E.Radford, and A.E.Ashcroft (2009).
HDX-ESI-MS reveals enhanced conformational dynamics of the amyloidogenic protein beta(2)-microglobulin upon release from the MHC-1.
  J Am Soc Mass Spectrom, 20, 278-286.  
20064447 O.Y.Borbulevych, K.H.Piepenbrink, B.E.Gloor, D.R.Scott, R.F.Sommese, D.K.Cole, A.K.Sewell, and B.M.Baker (2009).
T cell receptor cross-reactivity directed by antigen-dependent tuning of peptide-MHC molecular flexibility.
  Immunity, 31, 885-896.
PDB codes: 3h7b 3h9h 3h9s 3ixa
19464197 T.Beddoe, Z.Chen, C.S.Clements, L.K.Ely, S.R.Bushell, J.P.Vivian, L.Kjer-Nielsen, S.S.Pang, M.A.Dunstone, Y.C.Liu, W.A.Macdonald, M.A.Perugini, M.C.Wilce, S.R.Burrows, A.W.Purcell, T.Tiganis, S.P.Bottomley, J.McCluskey, and J.Rossjohn (2009).
Antigen ligation triggers a conformational change within the constant domain of the alphabeta T cell receptor.
  Immunity, 30, 777-788.  
18275824 J.H.Wang, R.J.Mallis, and E.L.Reinherz (2008).
Immunodominant-peptide recognition: beta testing TCRalphabeta.
  Immunity, 28, 139-141.  
18800968 K.M.Armstrong, K.H.Piepenbrink, and B.M.Baker (2008).
Conformational changes and flexibility in T-cell receptor recognition of peptide-MHC complexes.
  Biochem J, 415, 183-196.  
18973345 L.L.Jones, L.A.Colf, A.J.Bankovich, J.D.Stone, Y.G.Gao, C.M.Chan, R.H.Huang, K.C.Garcia, and D.M.Kranz (2008).
Different thermodynamic binding mechanisms and peptide fine specificities associated with a panel of structurally similar high-affinity T cell receptors.
  Biochemistry, 47, 12398-12408.
PDB code: 3ery
  18941216 L.L.Jones, L.A.Colf, J.D.Stone, K.C.Garcia, and D.M.Kranz (2008).
Distinct CDR3 conformations in TCRs determine the level of cross-reactivity for diverse antigens, but not the docking orientation.
  J Immunol, 181, 6255-6264.
PDB codes: 3e2h 3e3q
  18981164 Y.N.Naumov, E.N.Naumova, M.B.Yassai, K.Kota, R.M.Welsh, and L.K.Selin (2008).
Multiple glycines in TCR alpha-chains determine clonally diverse nature of human T cell memory to influenza A virus.
  J Immunol, 181, 7407-7419.  
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 code is shown on the right.

 

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