Travis Beddoe, Zhenjun Chen, Craig S. Clements, Lauren K. Ely, Simon R. ... Tony Tiganis, Stephen P. Bottomley, James McCluskey, and Jamie Rossjohn.
Immunity, Volume 30
Supplemental Data Antigen Ligation Triggers a Conformational Change within the Constant Domain of the αβ T Cell Receptor Travis Beddoe, Zhenjun Chen, Craig S. Clements, Lauren K. Ely, Simon R. Bushell, Julian P. Vivian, Lars Kjer-Nielsen, Siew Siew Pang, Michelle A. Dunstone, Yu Chih Liu, Whitney A. Macdonald, Matthew A. Perugini, Matthew C.J. Wilce, Scott R. Burrows, Anthony W. Purcell, Tony Tiganis, Stephen P. Bottomley, James McCluskey, and Jamie Rossjohn
Figure S1. CD69 upregulation of Jurkat transfectants As in Fig 5b, with normalised data
Immunity, Volume 30
Table S1. Crystallographic table and A-B loop conformation
The table below summarizes the differing conformations of the A-B loop observed in the structures of αβ TCRs that have been determined to date, in the liganded and/or non-liganded state. Only the structures of TCRs in which the complete ectodomains (namely variable and constant domains) are reported within this table. The relatively low resolution of the TCR-pMHC complexes, errors in model-building, crystal-packing effects, the poorly resolved electron-density of the A-B loop, and the high mobility of the A-B loop in some TCR-pMHC structures can potentially mask the conformation of the A-B loop. Nevertheless, the analyses shows that the A-B loop has the propensity to exist in two conformational states, which has been termed open and closed as per main body of the text, and this is broadly correlated with the liganded and non-liganded state of the TCR respectively.
Immunity, Volume 30
TCR LC13 LC13 ELS4 ELS4 1G4 1G4 E8 E8 2C 2C NKT15 NKT15 B7 JM22 AHIII12.2 KK50.4 SB27 HA1.7 HA1.7 3A6 ob.1A12 A6 A6
abcde+#-
MHC
Ligand
PDBID
MHCclass
AB-loop visibility
HLA-B8 HLA-B35 HLA-A2 HLA-DR1 H-2KBM3 CD1d HLA-A2 HLA-A2 HLA-A2 HLA-E HLA-B35 HLA-DR1 HLA-DR4 HLADR2a HLADR2b HLA-A2 HLA-A2
EBV(FLR)a EBV(EPL)a NY-ESOa TPI peptidec dEV8c α-galactosylceramide a TAXb MP(GIL)a p1049a UL40(VMA)c EBV(LPE)a HAa HAa MBPa
1KGC 1MI5 2NW2 2NX5 2BNU 2BNR 2IAL 2IAN 1TCR 1MWA 2EYT 2PO6 1BD2 1OGA 1LP9 2ESV 2AK4 1FYT 1J8H 1ZGL
I I I I I I II II I I CD1d CD1d I I I I I II II II
MBPa
1YMM
II
Yes Yes Missing 133-134 Yes Yes Yes Missing 123- 126 Yes Missing 130-131 Missing 130- 131 Yes Yes Missing 131-136 Yes Missing 130 -131 Yes Yes Missing 130- 132 Missing 130- 132 Missing 124 127 and 133 to 136 no
TAXb TAX(P6A)e
1AO7 1QRN
I I
no Yes
Loop description+ Closed Open Disordered Open Intermediate Open Disordered Open Open Open Closed Open Disordered Open Open Open ambiguous Disordered Disordered Disordered
Crystal contacts# No No Yes Yes No Yes No No Yes Yes Yes Yes No Yes No No Yes No No No
Disordered
No
Cα disordered Closed
No No
agonist strong agonist weak agonist superagonist weak antagonist see text for loop description symmetry contacts are defined as direct contacts between any atom within the A-B loop (residues 127 to 140) and any symmetry-related atom within 3.6 Å.
Immunity, Volume 30
References: 1) Kjer-Nielsen, L. et al. The 1.5 A crystal structure of a highly selected antiviral T cell receptor provides evidence for a structural basis of immunodominance. Structure 10, 1521-1532 (2002) 2) Kjer-Nielsen, L. et al. A structural basis for the selection of dominant alphabeta T cell receptors in antiviral immunity. Immunity 18, 53-64 (2003) 3) Tynan, F.E. et al. A T cell receptor flattens a bulged antigenic peptide presented by a major histocompatibility complex class I molecule. Nat. Immunol. 8, 268276 (2007) 4) Chen, J.-L. et al. Structural and kinetic basis for heightened immunogenicity of T cell vaccines. J. Exp. Med. 201, 1243-1255 (2005) 5) Dunn, S.M. et al. Directed evolution of human T cell receptor CDR2 residues by phage display dramatically enhances affinity for cognate peptide-MHC without increasing apparent cross-reactivity. Protein Sci. 15 710-721 (2006) 6) Deng, L. et al. Structural basis for the recognition of mutant self by a tumor-specific, MHC class II-restricted T cell receptor. Nat. Immunol. 8, 398-408 (2007) 7) Garcia, K.C. et al. An alphabeta T cell receptor structure at 2.5 A and its orientation in the TCR-MHC complex. Science 274, 209-219 (1996) 8) Luz, J.G. et al. Structural comparison of allogeneic and syngeneic T cell receptor-peptide-major histocompatibility complex complexes: a buried alloreactive mutation subtly alters peptide presentation substantially increasing V(beta) Interactions. J. Exp. Med. 195, 1175-1186 (2002) 9) Garcia, K.C. et al. Structural basis of plasticity in T cell receptor recognition of a self peptide-MHC antigen. Science 279, 1166-1172 (1998) 10) Degano, M. et al. A functional hot spot for antigen recognition in a superagonist TCR/MHC complex. Immunity 12, 251-261 (2000) 11) Kjer-Nielsen, L. et al. 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 (2006) 12) Borg, N.A. et al. CD1d-lipid-antigen recognition by the semi-invariant NKT T-cell receptor. Nature 448, 44-49 (2007) 13) Ding, Y.H. et al. Two human T cell receptors bind in a similar diagonal mode to the HLA-A2/Tax peptide complex using different TCR amino acids. Immunity 8, 403-411 (1998) 14) Stewart-Jones, G.B.E., Mcmichael, A.J., Bell, J.I., Stuart, D.I. & Jones, E.Y. A structural basis for immunodominant human T cell receptor recognition. Nat. Immunol. 4, 657-663 (2003) 15) Buslepp, J., Wang, H., Biddison, W.E., Appella, E. & Collins, E.J. A correlation between TCR Valpha docking on MHC and CD8 dependence: implications for T cell selection. Immunity 19, 595-606 (2003) 16) Hoare, H.L. et al. Structural basis for a major histocompatibility complex class Ib-restricted T cell response. Nat. Immunol. 7, 256-264 (2006) 17) Tynan, F.E. et al. T cell receptor recognition of a 'super-bulged' major histocompatibility complex class I-bound peptide. Nat. Immunol. 6, 1114-1122 (2005) 18) Hennecke, J., Carfi, A. & Wiley, D.C. Structure of a covalently stabilized complex of a human alphabeta T-cell receptor, influenza HA peptide and MHC class II molecule, HLA-DR1. EMBO J. 19, 5611-5624 (2000) 19) Hennecke, J. & Wiley, D.C. Structure of a complex of the human alpha/beta T cell receptor (TCR) HA1.7, influenza hemagglutinin peptide, and major histocompatibility complex class II molecule, HLA-DR4 (DRA*0101 and DRB1*0401): insight into TCR cross-restriction and alloreactivity. J. Exp. Med. 195, 571-581 (2002) 20) Li, Y. et al. Structure of a human autoimmune TCR bound to a myelin basic protein self-peptide and a multiple sclerosis-associated MHC class II molecule. EMBO J. 24, 2968-2979 (2005) 21) Hahn, M., Nicholson, M.J., Pyrdol, J. & Wucherpfennig, K.W. Unconventional topology of self peptide-major histocompatibility complex binding by a human autoimmune T cell receptor. Nat. Immunol. 6, 490-496 (2005) 22) Garboczi, D.N. et al. Structure of the complex between human T-cell receptor, viral peptide and HLA-A2. Nature 384, 134-141 (1996)
Immunity, Volume 30
23) Ding, Y.H., Baker, B.M., Garboczi, D.N., Biddison, W.E. & Wiley, D.C. Four A6-TCR/peptide/HLA-A2 structures that generate very different T cell signals are nearly identical. Immunity 11, 45-56 (1999) 24) Gagnon, S.J. et al. T cell receptor recognition via cooperative conformational plasticity. J.Mol.Biol. 363, 228-243 (2006)
