2ian
From Proteopedia
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Structural basis for recognition of mutant self by a tumor-specific, MHC class II-restricted TCR
Contents |
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.
Disease
Known diseases associated with this structure: Hemolytic anemia due to triosephosphate isomerase deficiency OMIM:[190450]
About this Structure
2IAN is a Protein complex structure of sequences from Homo sapiens. Active as Triose-phosphate isomerase, with EC number 5.3.1.1 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 Mon Nov 12 22:42:53 2007
