PDBsum entry 1zhk

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Immune system PDB id
Protein chains
276 a.a. *
99 a.a. *
13 a.a. *
Waters ×448
* Residue conservation analysis
PDB id:
Name: Immune system
Title: Crystal structure of hla-b 3501 Presenting 13-mer ebv antige lpeplpqgqltay
Structure: Hla class i histocompatibility antigen, b-35 alph chain: a. Fragment: extracellular domains alpha 1. Synonym: mhc heavy chain hla-b 3501, Mhc class i antigen b Engineered: yes. Beta-2-microglobulin. Chain: b. Synonym: hdcma22p. Engineered: yes.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: synthetic peptide lpeplpqgqltay
Biol. unit: Trimer (from PQS)
1.60Å     R-factor:   0.219     R-free:   0.231
Authors: F.E.Tynan,N.A.Borg,J.J.Miles,T.Beddoe,D.El-Hassen,S.L.Silins Zuylen,A.W.Purcell,L.Kjer-Nielsen,J.Mccluskey,S.R.Burrows,J
Key ref:
F.E.Tynan et al. (2005). High resolution structures of highly bulged viral epitopes bound to major histocompatibility complex class I. Implications for T-cell receptor engagement and T-cell immunodominance. J Biol Chem, 280, 23900-23909. PubMed id: 15849183 DOI: 10.1074/jbc.M503060200
26-Apr-05     Release date:   17-May-05    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P30685  (1B35_HUMAN) -  HLA class I histocompatibility antigen, B-35 alpha chain
362 a.a.
276 a.a.
Protein chain
Pfam   ArchSchema ?
P61769  (B2MG_HUMAN) -  Beta-2-microglobulin
119 a.a.
99 a.a.
Protein chain
No UniProt id for this chain
Struc: 13 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   16 terms 
  Biological process     immune system process   22 terms 
  Biochemical function     protein binding     3 terms  


DOI no: 10.1074/jbc.M503060200 J Biol Chem 280:23900-23909 (2005)
PubMed id: 15849183  
High resolution structures of highly bulged viral epitopes bound to major histocompatibility complex class I. Implications for T-cell receptor engagement and T-cell immunodominance.
F.E.Tynan, N.A.Borg, J.J.Miles, T.Beddoe, D.El-Hassen, S.L.Silins, W.J.van Zuylen, A.W.Purcell, L.Kjer-Nielsen, J.McCluskey, S.R.Burrows, J.Rossjohn.
Although HLA class I alleles can bind epitopes up to 14 amino acids in length, little is known about the immunogenicity or the responding T-cell repertoire against such determinants. Here, we describe an HLA-B*3508-restricted cytotoxic T lymphocyte response to a 13-mer viral epitope (LPEPLPQGQLTAY). The rigid, centrally bulged epitope generated a biased T-cell response. Only the N-terminal face of the peptide bulge was critical for recognition by the dominant clonotype SB27. The SB27 public T-cell receptor (TcR) associated slowly onto the complex between the bulged peptide and the major histocompatibility complex, suggesting significant remodeling upon engagement. The broad antigen-binding cleft of HLA-B*3508 represents a critical feature for engagement of the public TcR, as the narrower binding cleft of HLA-B*3501(LPEPLPQGQLTAY), which differs from HLA-B*3508 by a single amino acid polymorphism (Arg156 --> Leu), interacted poorly with the dominant TcR. Biased TcR usage in this cytotoxic T lymphocyte response appears to reflect a dominant role of the prominent peptide x major histocompatibility complex class I surface.
  Selected figure(s)  
Figure 1.
FIG. 1. Structures of bulged epitopes complexed to MHC-I. 2F[o] - F[c] electron density is shown in mesh format, with residues shown in ball-and-stick format. The polymorphic residue is shown in purple. A water molecule bridging the bulged loop is shown. A and B, structures of HLA-B^*3508 and HLA-B^*3501, respectively, complexed to LPEPLPQGQLTAY. C, superposition of the bulged epitopes bound to MHC-I compared with an 8-mer epitope. The 13-mer (this work) is shown in yellow, and the 8-mer peptide (45) shown in green. The MTF-E epitope is observed in two different conformations (25), shown in purple and orange.
Figure 2.
FIG. 2. A, superposition of the two antigen-binding clefts, HLA-B^*3508 (yellow) and HLA-B^*3501 (blue), highlighting the shift in the 2 helix spanning residues 145-158. B and C, impact of the polymorphism at position on the local structure of HLA-B^*3508^LPEPLPQGQLTAY and HLA-B^*3501^LPEPLPQGQLTAY, respectively. Residues are in ball-and-stick format. Polar interactions are depicted as dotted lines. The polymorphic residue is shown in green, and the peptide is shown in yellow.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 23900-23909) copyright 2005.  
  Figures were selected by the author.  

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
21067543 D.R.Flower, I.K.Macdonald, K.Ramakrishnan, M.N.Davies, and I.A.Doytchinova (2010).
Computer aided selection of candidate vaccine antigens.
  Immunome Res, 6, S1.  
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
20190139 L.Wooldridge, M.Clement, A.Lissina, E.S.Edwards, K.Ladell, J.Ekeruche, R.E.Hewitt, B.Laugel, E.Gostick, D.K.Cole, R.Debets, C.Berrevoets, J.J.Miles, S.R.Burrows, D.A.Price, and A.K.Sewell (2010).
MHC class I molecules with Superenhanced CD8 binding properties bypass the requirement for cognate TCR recognition and nonspecifically activate CTLs.
  J Immunol, 184, 3357-3366.  
20122941 N.G.Walpole, L.Kjer-Nielsen, L.Kostenko, J.McCluskey, A.G.Brooks, J.Rossjohn, and C.S.Clements (2010).
The structure and stability of the monomorphic HLA-G are influenced by the nature of the bound peptide.
  J Mol Biol, 397, 467-480.
PDB codes: 3kyn 3kyo
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
19605354 D.K.Cole, F.Yuan, P.J.Rizkallah, J.J.Miles, E.Gostick, D.A.Price, G.F.Gao, B.K.Jakobsen, and A.K.Sewell (2009).
Germ line-governed recognition of a cancer epitope by an immunodominant human T-cell receptor.
  J Biol Chem, 284, 27281-27289.
PDB code: 3hg1
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
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
  19177349 P.Kumar, A.Vahedi-Faridi, W.Saenger, A.Ziegler, and B.Uchanska-Ziegler (2009).
Conformational changes within the HLA-A1:MAGE-A1 complex induced by binding of a recombinant antibody fragment with TCR-like specificity.
  Protein Sci, 18, 37-49.
PDB code: 3bo8
19838694 V.Thammavongsa, M.Schaefer, T.Filzen, K.L.Collins, M.Carrington, N.Bangia, and M.Raghavan (2009).
Assembly and intracellular trafficking of HLA-B*3501 and HLA-B*3503.
  Immunogenetics, 61, 703-716.  
19000137 Y.H.Sohn, H.B.Oh, Y.S.Heo, and O.J.Kwon (2009).
Structural aspects of B*4617 molecule, a novel HLA-B*46 allele identified by sequence-based typing.
  Tissue Antigens, 73, 72-74.  
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.  
18378495 J.K.Archbold, W.A.Macdonald, S.R.Burrows, J.Rossjohn, and J.McCluskey (2008).
T-cell allorecognition: a case of mistaken identity or déjà vu?
  Trends Immunol, 29, 220-226.  
18270323 K.K.Wynn, Z.Fulton, L.Cooper, S.L.Silins, S.Gras, J.K.Archbold, F.E.Tynan, J.J.Miles, J.McCluskey, S.R.Burrows, J.Rossjohn, and R.Khanna (2008).
Impact of clonal competition for peptide-MHC complexes on the CD8+ T-cell repertoire selection in a persistent viral infection.
  Blood, 111, 4283-4292.
PDB codes: 3bw9 3bwa
17719639 K.Kedzierska, N.L.La Gruta, J.Stambas, S.J.Turner, and P.C.Doherty (2008).
Tracking phenotypically and functionally distinct T cell subsets via T cell repertoire diversity.
  Mol Immunol, 45, 607-618.  
18612635 M.A.Sherman, R.M.Goto, R.E.Moore, H.D.Hunt, T.D.Lee, and M.M.Miller (2008).
Mass spectral data for 64 eluted peptides and structural modeling define peptide binding preferences for class I alleles in two chicken MHC-B haplotypes associated with opposite responses to Marek's disease.
  Immunogenetics, 60, 527-541.  
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.  
17378764 A.D.Hislop, G.S.Taylor, D.Sauce, and A.B.Rickinson (2007).
Cellular responses to viral infection in humans: lessons from Epstein-Barr virus.
  Annu Rev Immunol, 25, 587-617.  
17473845 A.W.Purcell, J.McCluskey, and J.Rossjohn (2007).
More than one reason to rethink the use of peptides in vaccine design.
  Nat Rev Drug Discov, 6, 404-414.  
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.  
17804503 X.G.Yu, M.Lichterfeld, K.L.Williams, J.Martinez-Picado, and B.D.Walker (2007).
Random T-cell receptor recruitment in human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T cells from genetically identical twins infected with the same HIV-1 strain.
  J Virol, 81, 12666-12669.  
17011774 C.S.Clements, M.A.Dunstone, W.A.Macdonald, J.McCluskey, and J.Rossjohn (2006).
Specificity on a knife-edge: the alphabeta T cell receptor.
  Curr Opin Struct Biol, 16, 787-795.  
16505140 L.Kjer-Nielsen, N.A.Borg, D.G.Pellicci, T.Beddoe, L.Kostenko, C.S.Clements, N.A.Williamson, M.J.Smyth, G.S.Besra, H.H.Reid, M.Bharadwaj, D.I.Godfrey, J.Rossjohn, and J.McCluskey (2006).
A structural basis for selection and cross-species reactivity of the semi-invariant NKT cell receptor in CD1d/glycolipid recognition.
  J Exp Med, 203, 661-673.
PDB codes: 2eyr 2eys 2eyt
16551255 M.G.Rudolph, R.L.Stanfield, and I.A.Wilson (2006).
How TCRs bind MHCs, peptides, and coreceptors.
  Annu Rev Immunol, 24, 419-466.  
17125150 R.L.Rich, and D.G.Myszka (2006).
Survey of the year 2005 commercial optical biosensor literature.
  J Mol Recognit, 19, 478-534.  
17110956 S.J.Turner, P.C.Doherty, J.McCluskey, and J.Rossjohn (2006).
Structural determinants of T-cell receptor bias in immunity.
  Nat Rev Immunol, 6, 883-894.  
16297661 S.R.Burrows, J.Rossjohn, and J.McCluskey (2006).
Have we cut ourselves too short in mapping CTL epitopes?
  Trends Immunol, 27, 11-16.  
  17142892 T.Blicher, J.S.Kastrup, L...Pedersen, S.Buus, and M.Gajhede (2006).
Structure of HLA-A*1101 in complex with a hepatitis B peptide homologue.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 1179-1184.
PDB code: 2hn7
16275762 F.E.Tynan, D.Elhassen, A.W.Purcell, J.M.Burrows, N.A.Borg, J.J.Miles, N.A.Williamson, K.J.Green, J.Tellam, L.Kjer-Nielsen, J.McCluskey, J.Rossjohn, and S.R.Burrows (2005).
The immunogenicity of a viral cytotoxic T cell epitope is controlled by its MHC-bound conformation.
  J Exp Med, 202, 1249-1260.
PDB codes: 2axf 2axg
16186824 F.E.Tynan, S.R.Burrows, A.M.Buckle, C.S.Clements, N.A.Borg, J.J.Miles, T.Beddoe, J.C.Whisstock, M.C.Wilce, S.L.Silins, J.M.Burrows, L.Kjer-Nielsen, L.Kostenko, A.W.Purcell, J.McCluskey, and J.Rossjohn (2005).
T cell receptor recognition of a 'super-bulged' major histocompatibility complex class I-bound peptide.
  Nat Immunol, 6, 1114-1122.
PDB code: 2ak4
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.