2IAL

Structural basis for recognition of mutant self by a tumor-specific, MHC class II-restricted TCR

Summary for 2IAL

• Entry DOI: 10.2210/pdb2ial/pdb
• Related: 1KLG 1KLU 2IAM 2IAN
• Descriptor: CD4+ T cell receptor E8 alpha chain, CD4+ T cell receptor E8 beta chain (3 entities in total)
• Functional Keywords: major histocompatibility complex, t cell receptor, t cell stimulation, melanoma, tumor antigen, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass membrane protein (Potential): P01848 P01850
• Total number of polymer chains: 4
• Total formula weight: 98975.76

Authors

Deng, L.,Langley, R.J.,Mariuzza, R.A. (deposition date: 2006-09-08, release date: 2007-04-03, Last modification date: 2024-11-13)

Primary citation

Deng, L.,Langley, R.J.,Brown, P.H.,Xu, G.,Teng, L.,Wang, Q.,Gonzales, M.I.,Callender, G.G.,Nishimura, M.I.,Topalian, S.L.,Mariuzza, R.A.
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

PubMed 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.

PubMed: 17334368
DOI: 10.1038/ni1447

Experimental method

X-RAY DIFFRACTION (1.92 Å)