Journal
NATURE IMMUNOLOGY
Volume 8, Issue 4, Pages 398-408Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni1447
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Funding
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R37AI036900, R01AI036900] Funding Source: NIH RePORTER
- Intramural NIH HHS Funding Source: Medline
- NIAID NIH HHS [R37 AI036900, AI036900] Funding Source: Medline
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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.
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