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PDBsum entry 2ian

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Immune system PDB id
2ian
Jmol
Contents
Protein chains
178 a.a.
181 a.a.
15 a.a.
198 a.a.
238 a.a.
Waters ×76

References listed in PDB file
Key reference
Title Structural basis for the recognition of mutant self by a tumor-Specific, Mhc class ii-Restricted t cell receptor.
Authors L.Deng, R.J.Langley, P.H.Brown, G.Xu, L.Teng, Q.Wang, M.I.Gonzales, G.G.Callender, M.I.Nishimura, S.L.Topalian, R.A.Mariuzza.
Ref. Nat Immunol, 2007, 8, 398-408. [DOI no: 10.1038/ni1447]
PubMed id 17334368
Abstract
Structural studies of complexes of T cell receptor (TCR) and peptide-major histocompatibility complex (MHC) have focused on TCRs specific for foreign antigens or native self. An unexplored category of TCRs includes those specific for self determinants bearing alterations resulting from disease, notably cancer. We determined here the structure of a human melanoma-specific TCR (E8) bound to the MHC molecule HLA-DR1 and an epitope from mutant triosephosphate isomerase. The structure had features intermediate between 'anti-foreign' and autoimmune TCR-peptide-MHC class II complexes that may reflect the hybrid nature of altered self. E8 manifested very low affinity for mutant triosephosphate isomerase-HLA-DR1 despite the highly tumor-reactive properties of E8 cells. A second TCR (G4) had even lower affinity but underwent peptide-specific formation of dimers, suggesting this as a mechanism for enhancing low-affinity TCR-peptide-MHC interactions for T cell activation.
Figure 4.
(a) TCR residues in contact with mutant TPI. The substituted TPI isoleucine residue (position 3) is magenta. (b) Interactions between E8 and mutant TPI. (c) Interactions between the E8 V[ ]domain and the HLA-DR1 1 -helix. (d,e) Interactions between mutant TPI isoleucine at position 3 and TCR E8 (d) or wild-type TPI threonine at position 3 and HLA-DR1 complexes (e). TCR residues are identified by one-letter amino-acid designation followed by position number and chain designation; peptide residues are identified by one-letter amino-acid designation followed by position ('P') number. Colors of TCR and MHC molecules as in Figure 3; hydrogen bonds, red dotted lines; salt bridges, solid lines; van der Waals contacts, black dotted lines.
Figure 6.
(a–c) Structural rearrangements in CDR2 , CDR3 and CDR3 induced by binding to mutant TPI–DR1. Bound E8, green; unbound E8, magenta; HLA-DR1, gold; mutant TPI, gray. Residues from E8 and DR1 involved in interactions with peptide are identified. (d) Superposition of mutant TPI–DR1 in a form without bound ligand (peptide, cyan; MHC, violet) and in complex with E8 (peptide, gray; MHC, gold). Arrow indicates residues 55–59 of the HLA-DR1 1 domain. (e) Conformational changes in TPI residues that contact E8. Residues of TPI involved in interactions with E8 are identified. Residue designations as in Figure 4.
The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Immunol (2007, 8, 398-408) copyright 2007.
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