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PDBsum entry 2axf
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Immune system/gene regulation PDB id
2axf

 

 

 

 

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Contents
Protein chains
276 a.a. *
99 a.a. *
Ligands
ALA-PRO-GLN-PRO-
ALA-PRO-GLU-ASN-
ALA-TYR
ACY ×2
Waters ×516
* Residue conservation analysis
PDB id:
2axf
Name: Immune system/gene regulation
Title: The immunogenicity of a viral cytotoxic t cell epitope is controlled by its mhc-bound conformation
Structure: Hla class i histocompatibility antigen, b 3508 Heavy chain. Chain: a. Fragment: residues 1-276. Synonym: hla-b 3508 Class i histocompatibility antigen, mhc class i antigen b 3508. Engineered: yes. Beta-2-microglobulin. Chain: b. 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 apqpapenay
Biol. unit: Trimer (from PQS)
Resolution:
1.80Å     R-factor:   0.208     R-free:   0.234
Authors: 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,S.R.Burrows
Key ref: F.E.Tynan et al. (2005). The immunogenicity of a viral cytotoxic T cell epitope is controlled by its MHC-bound conformation. J Exp Med, 202, 1249-1260. PubMed id: 16275762
Date:
05-Sep-05     Release date:   29-Nov-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P01889  (1B07_HUMAN) -  HLA class I histocompatibility antigen, B alpha chain from Homo sapiens
Seq:
Struc: 		362 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
* PDB and UniProt seqs differ at 21 residue positions (black crosses)

 

 
J Exp Med 202:1249-1260 (2005)
PubMed id: 16275762  
 
 
The immunogenicity of a viral cytotoxic T cell epitope is controlled by its MHC-bound conformation.
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, S.R.Burrows.
 
  ABSTRACT  
 
Thousands of potentially antigenic peptides are encoded by an infecting pathogen; however, only a small proportion induce measurable CD8(+) T cell responses. To investigate the factors that control peptide immunogenicity, we have examined the cytotoxic T lymphocyte (CTL) response to a previously undefined epitope ((77)APQPAPENAY(86)) from the BZLF1 protein of Epstein-Barr virus (EBV). This peptide binds well to two human histocompatibility leukocyte antigen (HLA) allotypes, HLA-B*3501 and HLA-B*3508, which differ by a single amino acid at position 156 ((156)Leucine vs. (156)Arginine, respectively). Surprisingly, only individuals expressing HLA-B*3508 show evidence of a CTL response to the (77)APQPAPENAY(86) epitope even though EBV-infected cells expressing HLA-B*3501 process and present similar amounts of peptide for CTL recognition, suggesting that factors other than peptide presentation levels are influencing immunogenicity. Functional and structural analysis revealed marked conformational differences in the peptide, when bound to each HLA-B35 allotype, that are dictated by the polymorphic HLA residue 156 and that directly affected T cell receptor recognition. These data indicate that the immunogenicity of an antigenic peptide is influenced not only by how well the peptide binds to major histocompatibility complex (MHC) molecules but also by its bound conformation. It also illustrates a novel mechanism through which MHC polymorphism can further diversify the immune response to infecting pathogens.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21365653 G.Luo, G.Quan, J.Guo, H.Zhang, S.Li, W.Wu, L.Nie, Y.Dong, S.Wu, G.Zheng, J.Yang, J.Xu, and W.Wang (2011).
A basic phenylalanine-rich oligo-peptide causes antibody cross-reactivity.
  Electrophoresis, 32, 752-763.  
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
19933168 D.R.Karp, N.Marthandan, S.G.Marsh, C.Ahn, F.C.Arnett, D.S.Deluca, A.D.Diehl, R.Dunivin, K.Eilbeck, M.Feolo, P.A.Guidry, W.Helmberg, S.Lewis, M.D.Mayes, C.Mungall, D.A.Natale, B.Peters, E.Petersdorf, J.D.Reveille, B.Smith, G.Thomson, M.J.Waller, and R.H.Scheuermann (2010).
Novel sequence feature variant type analysis of the HLA genetic association in systemic sclerosis.
  Hum Mol Genet, 19, 707-719.  
19449168 E.Hassen, G.Nahla, N.Bouaouina, and L.Chouchane (2010).
The human leukocyte antigen class I genes in nasopharyngeal carcinoma risk.
  Mol Biol Rep, 37, 119-126.  
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
20536911 S.H.Hwang, H.B.Oh, S.E.Choi, J.J.Seo, J.H.Lee, S.W.Cho, J.M.Chae, Y.S.Heo, C.L.Chang, and E.Y.Lee (2010).
Impact of amino acid substitution at residue 9 of HLA-A2 on the development of acute GVHD in Korean pediatric patients receiving unrelated hematopoietic stem cell transplantation.
  Transpl Int, 23, 1216-1222.  
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
19664630 F.Y.Sung, C.M.Jung, C.F.Wu, C.L.Lin, C.J.Liu, Y.F.Liaw, K.S.Tsai, and M.W.Yu (2009).
Hepatitis B virus core variants modify natural course of viral infection and hepatocellular carcinoma progression.
  Gastroenterology, 137, 1687-1697.  
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
19015225 M.P.Pender, P.A.Csurhes, A.Lenarczyk, C.M.Pfluger, and S.R.Burrows (2009).
Decreased T cell reactivity to Epstein-Barr virus infected lymphoblastoid cell lines in multiple sclerosis.
  J Neurol Neurosurg Psychiatry, 80, 498-505.  
19254880 M.P.Pender (2009).
Preventing and curing multiple sclerosis by controlling Epstein-Barr virus infection.
  Autoimmun Rev, 8, 563-568.  
19617632 P.Kumar, A.Vahedi-Faridi, W.Saenger, E.Merino, J.A.López de Castro, B.Uchanska-Ziegler, and A.Ziegler (2009).
Structural basis for T cell alloreactivity among three HLA-B14 and HLA-B27 antigens.
  J Biol Chem, 284, 29784-29797.
PDB codes: 3bp4 3bp7 3bvn 3bxn
18997170 T.Kawase, K.Matsuo, K.Kashiwase, H.Inoko, H.Saji, S.Ogawa, S.Kato, T.Sasazuki, Y.Kodera, and Y.Morishima (2009).
HLA mismatch combinations associated with decreased risk of relapse: implications for the molecular mechanism.
  Blood, 113, 2851-2858.  
18799575 A.T.Tan, E.Loggi, C.Boni, A.Chia, A.J.Gehring, K.S.Sastry, V.Goh, P.Fisicaro, P.Andreone, C.Brander, S.G.Lim, C.Ferrari, F.Bihl, and A.Bertoletti (2008).
Host ethnicity and virus genotype shape the hepatitis B virus-specific T-cell repertoire.
  J Virol, 82, 10986-10997.  
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.  
18245836 R.J.Stoffels, and H.G.Spencer (2008).
An asymmetric model of heterozygote advantage at major histocompatibility complex genes: degenerate pathogen recognition and intersection advantage.
  Genetics, 178, 1473-1489.  
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.  
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.  
17096150 D.Godelaine, J.Carrasco, F.Brasseur, B.Neyns, K.Thielemans, T.Boon, and A.Van Pel (2007).
A new tumor-specific antigen encoded by MAGE-C2 and presented to cytolytic T lymphocytes by HLA-B44.
  Cancer Immunol Immunother, 56, 753-759.  
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
17459809 G.E.Hammer, T.Kanaseki, and N.Shastri (2007).
The final touches make perfect the peptide-MHC class I repertoire.
  Immunity, 26, 397-406.  
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.  
17496542 S.Terakura, M.Murata, E.H.Warren, A.Sette, J.Sidney, T.Naoe, and S.R.Riddell (2007).
A single minor histocompatibility antigen encoded by UGT2B17 and presented by human leukocyte antigen-A*2902 and -B*4403.
  Transplantation, 83, 1242-1248.  
17121793 X.G.Yu, M.Lichterfeld, S.Chetty, K.L.Williams, S.K.Mui, T.Miura, N.Frahm, M.E.Feeney, Y.Tang, F.Pereyra, M.X.Labute, K.Pfafferott, A.Leslie, H.Crawford, R.Allgaier, W.Hildebrand, R.Kaslow, C.Brander, T.M.Allen, E.S.Rosenberg, P.Kiepiela, M.Vajpayee, P.A.Goepfert, M.Altfeld, P.J.Goulder, and B.D.Walker (2007).
Mutually exclusive T-cell receptor induction and differential susceptibility to human immunodeficiency virus type 1 mutational escape associated with a two-amino-acid difference between HLA class I subtypes.
  J Virol, 81, 1619-1631.  
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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