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

 

 

 

 

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Contents
Protein chains
202 a.a. *
243 a.a. *
Waters ×32
* Residue conservation analysis
PDB id:
2eyt
Name: Immune system
Title: A structural basis for selection and cross-species reactivity of the semi-invariant nkt cell receptor in cd1d/glycolipid recognition
Structure: Nkt15. Chain: a, c. Engineered: yes. Nkt15. Chain: b, d. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PQS)
Resolution:
2.60Å     R-factor:   0.210     R-free:   0.256
Authors: L.Kjer-Nielsen,N.A.Borg
Key ref: L.Kjer-Nielsen et al. (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. PubMed id: 16505140
Date:
09-Nov-05     Release date:   21-Mar-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P01848  (TCA_HUMAN) -  T cell receptor alpha chain constant from Homo sapiens
Seq:
Struc: 		140 a.a.
202 a.a.*
Protein chains
Pfam   ArchSchema ?
A0A5B9  (TRBC2_HUMAN) -  T cell receptor beta constant 2 from Homo sapiens
Seq:
Struc: 		178 a.a.
243 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 

 
J Exp Med 203:661-673 (2006)
PubMed id: 16505140  
 
 
A structural basis for selection and cross-species reactivity of the semi-invariant NKT cell receptor in CD1d/glycolipid recognition.
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, J.McCluskey.
 
  ABSTRACT  
 
Little is known regarding the basis for selection of the semi-invariant alphabeta T cell receptor (TCR) expressed by natural killer T (NKT) cells or how this mediates recognition of CD1d-glycolipid complexes. We have determined the structures of two human NKT TCRs that differ in their CDR3beta composition and length. Both TCRs contain a conserved, positively charged pocket at the ligand interface that is lined by residues from the invariant TCR alpha- and semi-invariant beta-chains. The cavity is centrally located and ideally suited to interact with the exposed glycosyl head group of glycolipid antigens. Sequences common to mouse and human invariant NKT TCRs reveal a contiguous conserved "hot spot" that provides a basis for the reactivity of NKT cells across species. Structural and functional data suggest that the CDR3beta loop provides a plasticity mechanism that accommodates recognition of a variety of glycolipid antigens presented by CD1d. We propose a model of NKT TCR-CD1d-glycolipid interaction in which the invariant CDR3alpha loop is predicted to play a major role in determining the inherent bias toward CD1d. The findings define a structural basis for the selection of the semi-invariant alphabeta TCR and the unique antigen specificity of NKT cells.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
23154222 J.Rossjohn, D.G.Pellicci, O.Patel, L.Gapin, and D.I.Godfrey (2012).
Recognition of CD1d-restricted antigens by natural killer T cells.
  Nat Rev Immunol, 12, 845-857.  
21298486 E.Champagne (2011).
γδ T cell Receptor Ligands and Modes of Antigen Recognition.
  Arch Immunol Ther Exp (Warsz), 59, 117-137.  
21376639 K.S.Wun, G.Cameron, O.Patel, S.S.Pang, D.G.Pellicci, L.C.Sullivan, S.Keshipeddy, M.H.Young, A.P.Uldrich, M.S.Thakur, S.K.Richardson, A.R.Howell, P.A.Illarionov, A.G.Brooks, G.S.Besra, J.McCluskey, L.Gapin, S.A.Porcelli, D.I.Godfrey, and J.Rossjohn (2011).
A molecular basis for the exquisite CD1d-restricted antigen specificity and functional responses of natural killer T cells.
  Immunity, 34, 327-339.
PDB codes: 3arb 3ard 3are 3arf 3arg
21376640 T.Mallevaey, A.J.Clarke, J.P.Scott-Browne, M.H.Young, L.C.Roisman, D.G.Pellicci, O.Patel, J.P.Vivian, J.L.Matsuda, J.McCluskey, D.I.Godfrey, P.Marrack, J.Rossjohn, and L.Gapin (2011).
A molecular basis for NKT cell recognition of CD1d-self-antigen.
  Immunity, 34, 315-326.
PDB codes: 3au1 3qi9
20404101 I.Engel, K.Hammond, B.A.Sullivan, X.He, I.Taniuchi, D.Kappes, and M.Kronenberg (2010).
Co-receptor choice by V alpha14i NKT cells is driven by Th-POK expression rather than avoidance of CD8-mediated negative selection.
  J Exp Med, 207, 1015-1029.  
20080535 J.Wang, Y.Li, Y.Kinjo, T.T.Mac, D.Gibson, G.F.Painter, M.Kronenberg, and D.M.Zajonc (2010).
Lipid binding orientation within CD1d affects recognition of Borrelia burgorferi antigens by NKT cells.
  Proc Natl Acad Sci U S A, 107, 1535-1540.
PDB codes: 3ilp 3ilq
20465577 S.Hegde, L.Fox, X.Wang, and J.E.Gumperz (2010).
Autoreactive natural killer T cells: promoting immune protection and immune tolerance through varied interactions with myeloid antigen-presenting cells.
  Immunology, 130, 471-483.  
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
19594637 D.M.Zajonc, and M.Kronenberg (2009).
Carbohydrate specificity of the recognition of diverse glycolipids by natural killer T cells.
  Immunol Rev, 230, 188-200.  
19185921 F.A.Looringh van Beeck, P.Reinink, R.Hermsen, D.M.Zajonc, M.J.Laven, A.Fun, M.Troskie, N.J.Schoemaker, D.Morar, J.A.Lenstra, L.Vervelde, V.P.Rutten, W.van Eden, and I.Van Rhijn (2009).
Functional CD1d and/or NKT cell invariant chain transcript in horse, pig, African elephant and guinea pig, but not in ruminants.
  Mol Immunol, 46, 1424-1431.  
19859526 L.M.Fox, D.G.Cox, J.L.Lockridge, X.Wang, X.Chen, L.Scharf, D.L.Trott, R.M.Ndonye, N.Veerapen, G.S.Besra, A.R.Howell, M.E.Cook, E.J.Adams, W.H.Hildebrand, and J.E.Gumperz (2009).
Recognition of lyso-phospholipids by human natural killer T lymphocytes.
  PLoS Biol, 7, e1000228.  
19416870 S.Huang, E.Martin, S.Kim, L.Yu, C.Soudais, D.H.Fremont, O.Lantz, and T.H.Hansen (2009).
MR1 antigen presentation to mucosal-associated invariant T cells was highly conserved in evolution.
  Proc Natl Acad Sci U S A, 106, 8290-8295.  
19592274 T.Mallevaey, J.P.Scott-Browne, J.L.Matsuda, M.H.Young, D.G.Pellicci, O.Patel, M.Thakur, L.Kjer-Nielsen, S.K.Richardson, V.Cerundolo, A.R.Howell, J.McCluskey, D.I.Godfrey, J.Rossjohn, P.Marrack, and L.Gapin (2009).
T cell receptor CDR2 beta and CDR3 beta loops collaborate functionally to shape the iNKT cell repertoire.
  Immunity, 31, 60-71.  
19816402 W.C.Florence, C.Xia, L.E.Gordy, W.Chen, Y.Zhang, J.Scott-Browne, Y.Kinjo, K.O.Yu, S.Keshipeddy, D.G.Pellicci, O.Patel, L.Kjer-Nielsen, J.McCluskey, D.I.Godfrey, J.Rossjohn, S.K.Richardson, S.A.Porcelli, A.R.Howell, K.Hayakawa, L.Gapin, D.M.Zajonc, P.G.Wang, and S.Joyce (2009).
Adaptability of the semi-invariant natural killer T-cell receptor towards structurally diverse CD1d-restricted ligands.
  EMBO J, 28, 3579-3590.  
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.  
18295796 D.M.Zajonc, P.B.Savage, A.Bendelac, I.A.Wilson, and L.Teyton (2008).
Crystal structures of mouse CD1d-iGb3 complex and its cognate Valpha14 T cell receptor suggest a model for dual recognition of foreign and self glycolipids.
  J Mol Biol, 377, 1104-1116.
PDB codes: 2q7y 2q86
18593354 J.D.Silk, M.Salio, J.Brown, E.Y.Jones, and V.Cerundolo (2008).
Structural and functional aspects of lipid binding by CD1 molecules.
  Annu Rev Cell Dev Biol, 24, 369-395.  
18378792 K.S.Wun, N.A.Borg, L.Kjer-Nielsen, T.Beddoe, R.Koh, S.K.Richardson, M.Thakur, A.R.Howell, J.P.Scott-Browne, L.Gapin, D.I.Godfrey, J.McCluskey, and J.Rossjohn (2008).
A minimal binding footprint on CD1d-glycolipid is a basis for selection of the unique human NKT TCR.
  J Exp Med, 205, 939-949.  
18304006 P.Marrack, J.P.Scott-Browne, S.Dai, L.Gapin, and J.W.Kappler (2008).
Evolutionarily conserved amino acids that control TCR-MHC interaction.
  Annu Rev Immunol, 26, 171-203.  
17150027 A.Bendelac, P.B.Savage, and L.Teyton (2007).
The biology of NKT cells.
  Annu Rev Immunol, 25, 297-336.  
17485514 C.McCarthy, D.Shepherd, S.Fleire, V.S.Stronge, M.Koch, P.A.Illarionov, G.Bossi, M.Salio, G.Denkberg, F.Reddington, A.Tarlton, B.G.Reddy, R.R.Schmidt, Y.Reiter, G.M.Griffiths, P.A.van der Merwe, G.S.Besra, E.Y.Jones, F.D.Batista, and V.Cerundolo (2007).
The length of lipids bound to human CD1d molecules modulates the affinity of NKT cell TCR and the threshold of NKT cell activation.
  J Exp Med, 204, 1131-1144.  
17581593 D.B.Moody (2007).
Immunology: how a T cell sees sugar.
  Nature, 448, 36-37.  
17589542 D.I.Godfrey, and S.P.Berzins (2007).
Control points in NKT-cell development.
  Nat Rev Immunol, 7, 505-518.  
17951048 D.M.Zajonc, and M.Kronenberg (2007).
CD1 mediated T cell recognition of glycolipids.
  Curr Opin Struct Biol, 17, 521-529.  
17828267 J.P.Scott-Browne, J.L.Matsuda, T.Mallevaey, J.White, N.A.Borg, J.McCluskey, J.Rossjohn, J.Kappler, P.Marrack, and L.Gapin (2007).
Germline-encoded recognition of diverse glycolipids by natural killer T cells.
  Nat Immunol, 8, 1105-1113.  
17607300 L.Yang, R.Jhaveri, J.Huang, Y.Qi, and A.M.Diehl (2007).
Endoplasmic reticulum stress, hepatocyte CD1d and NKT cell abnormalities in murine fatty livers.
  Lab Invest, 87, 927-937.  
17581592 N.A.Borg, K.S.Wun, L.Kjer-Nielsen, M.C.Wilce, D.G.Pellicci, R.Koh, G.S.Besra, M.Bharadwaj, D.I.Godfrey, J.McCluskey, and J.Rossjohn (2007).
CD1d-lipid-antigen recognition by the semi-invariant NKT T-cell receptor.
  Nature, 448, 44-49.
PDB code: 2po6
18074396 R.L.Rich, and D.G.Myszka (2007).
Survey of the year 2006 commercial optical biosensor literature.
  J Mol Recognit, 20, 300-366.  
16855607 D.B.Moody (2006).
TLR gateways to CD1 function.
  Nat Immunol, 7, 811-817.  
16870416 E.Treiner, and O.Lantz (2006).
CD1d- and MR1-restricted invariant T cells: of mice and men.
  Curr Opin Immunol, 18, 519-526.  
17661645 G.Wingender, and M.Kronenberg (2006).
Invariant natural killer cells in the response to bacteria: the advent of specific antigens.
  Future Microbiol, 1, 325-340.  
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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