PDB 2IAN deposited: 2006-09-08 modified: 2009-02-24
Title Structural basis for recognition of mutant self by a tumor-specific, MHC class II-restricted TCR
Authors Brown, P.H., Callender, G.G., Deng, L., Gonzales, M.I., Langley, R.J., Mariuzza, R.A., Nishimura, M.I., Teng, L., Topalian, S.L., Wang, Q., Xu, G.
Structure factors resolution 2.8 rfactor 0.22116 rfree 0.2959
DPI 1.00 theoretical min: 0.55
Related PDB Entries 2IAL 2IAM

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.

Nat.Immunol. 2007 Apr; 8(4):398-408 doi:10.1038/ni1447

Cross References
Database source Identifier Description
PubMed 17334368
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
2IAN/1 2IAN 1 pentamer 0 5 0 6031
2IAN/2 2IAN 2 pentamer 0 5 0 6098
2IAN/3 2IAN 3 pentamer 0 5 0 6098
2IAN/4 2IAN 4 pentamer 0 5 0 6080