2ial
From Proteopedia
Structural basis for recognition of mutant self by a tumor-specific, MHC class II-restricted TCR
Overview
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.
About this Structure
Full crystallographic information is available from OCA.
Reference
Structural basis for the recognition of mutant self by a tumor-specific, MHC class II-restricted T cell receptor., Deng L, Langley RJ, Brown PH, Xu G, Teng L, Wang Q, Gonzales MI, Callender GG, Nishimura MI, Topalian SL, Mariuzza RA, Nat Immunol. 2007 Apr;8(4):398-408. Epub 2007 Mar 4. PMID:17334368 Page seeded by OCA on Sun May 4 07:16:05 2008
