PDBsum entry 1i7u

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Immune system PDB id
Protein chains
275 a.a. *
100 a.a. *
Waters ×489
* Residue conservation analysis
PDB id:
Name: Immune system
Title: Crystal structure of class i mhc a2 in complex with peptide p1049-6v
Structure: Hla class i histocompatibility antigen, a-2 alpha chain. Chain: a, d. Fragment: extracellular domain, residues 25-299. Engineered: yes. Beta-2-microglobulin. Chain: b, e. Engineered: yes. 9 residue peptide.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: hlaa. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Gene: b2m. Synthetic: yes. Other_details: the nine residue peptide was chemically
Biol. unit: Trimer (from PQS)
1.80Å     R-factor:   0.237     R-free:   0.258
Authors: J.Busslep,R.Zhao,D.Loftus,E.Appella,E.J.Collins
Key ref:
J.Buslepp et al. (2001). T cell activity correlates with oligomeric peptide-major histocompatibility complex binding on T cell surface. J Biol Chem, 276, 47320-47328. PubMed id: 11584024 DOI: 10.1074/jbc.M109231200
10-Mar-01     Release date:   24-Oct-01    
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Protein chains
Pfam   ArchSchema ?
P01892  (1A02_HUMAN) -  HLA class I histocompatibility antigen, A-2 alpha chain
365 a.a.
275 a.a.
Protein chains
Pfam   ArchSchema ?
P61769  (B2MG_HUMAN) -  Beta-2-microglobulin
119 a.a.
100 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 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.M109231200 J Biol Chem 276:47320-47328 (2001)
PubMed id: 11584024  
T cell activity correlates with oligomeric peptide-major histocompatibility complex binding on T cell surface.
J.Buslepp, R.Zhao, D.Donnini, D.Loftus, M.Saad, E.Appella, E.J.Collins.
Recognition of virally infected cells by CD8+ T cells requires differentiation between self and nonself peptide-class I major histocompatibility complexes (pMHC). Recognition of foreign pMHC by host T cells is a major factor in the rejection of transplanted organs from the same species (allotransplant) or different species (xenotransplant). AHIII12.2 is a murine T cell clone that recognizes the xenogeneic (human) class I MHC HLA-A2.1 molecule (A2) and the syngeneic murine class I MHC H-2 D(b) molecule (D(b)). Recognition of both A2 and D(b) are peptide-dependent, and the sequences of the peptides recognized have been determined. Alterations in the antigenic peptides bound to A2 cause large changes in AHIII12.2 T cell responsiveness. Crystal structures of three representative peptides (agonist, null, and antagonist) bound to A2 partially explain the changes in AHIII12.2 responsiveness. Using class I pMHC octamers, a strong correlation is seen between T cell activity and the affinity of pMHC complexes for the T cell receptor. However, contrary to previous studies, we see similar half-lives for the pMHC multimers bound to the AHIII12.2 cell surface.
  Selected figure(s)  
Figure 2.
Fig. 2. T cell outcome does not correlate with peptide binding to HLA-A2.1. A, binding to cell surface A2 on T2 cells shows no correlation with biological activity. T2 cells incubated with the indicated concentration of peptide overnight were stained with BB7.2 and visualized by flow cytometry. p1049 ( ), p1049-A1F ( ), p1049-V8T ( ), p1049-W3P ( circle ), p1058 ( ), p1058-Y8T ( ), and p1058-P3W (×) are shown. B, a scattergram of CTL activity versus relative binding capacity (K[r]) shows the lack of correlation (R value 0.0961). C, cell surface half-life assay shows no correlation with T cell outcome. Brefeldin A-treated T2 cells pulsed with peptide were stained with BB7.2 at the indicated times. The amount of A2 remaining on the cell surface over time was visualized by flow cytometry. p1049 ( ), t = 20 h; p1049-F5V ( ), t = >40.0 h; p1049-F6V ( ), t = >40.0 h; p1049-A1F/V8Y ( ), t = 32.7 h; p1058 ( ), t = 1.3 h.
Figure 3.
Fig. 3. Crystal structures of altered peptides bound to A2 show similar main chain paths and small side chain differences. The comparison of peptides after superpositioning of each peptide-binding groove shows small changes that result as a consequence of amino acid substitutions. The class I MHC molecules are removed for clarity; this is justified because the MHC structure is virtually identical between the complexes. Superpositions are shown of the following. A, agonist p1049 (cyan) and antagonist p1058 (magenta); B, agonist p1049 (cyan) and null peptide p1049-F5V (yellow); C, agonist p1049 (cyan) and agonist p1049-F6V (silver). D, superpositions of p1058 (magenta) bound to A2 and p1027 (blue) bound to H2D^b (26) shows that the conformation of the peptide has more to do with the MHC than the sequence of the peptide. Images were made with GRASP (45).
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2001, 276, 47320-47328) copyright 2001.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
20442757 D.A.Antunes, G.F.Vieira, M.M.Rigo, S.P.Cibulski, M.Sinigaglia, and J.A.Chies (2010).
Structural allele-specific patterns adopted by epitopes in the MHC-I cleft and reconstruction of MHC:peptide complexes to cross-reactivity assessment.
  PLoS One, 5, e10353.  
16470819 A.J.Bordner, and R.Abagyan (2006).
Ab initio prediction of peptide-MHC binding geometry for diverse class I MHC allotypes.
  Proteins, 63, 512-526.  
15583017 J.K.Lee, G.Stewart-Jones, T.Dong, K.Harlos, K.Di Gleria, L.Dorrell, D.C.Douek, P.A.van der Merwe, E.Y.Jones, and A.J.McMichael (2004).
T cell cross-reactivity and conformational changes during TCR engagement.
  J Exp Med, 200, 1455-1466.
PDB codes: 2bsu 2bsv 2v2w 2v2x
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