Document Detail

Structural basis for the recognition of mutant self by a tumor-specific, MHC class II-restricted T cell receptor.
MedLine Citation:
PMID:  17334368     Owner:  NLM     Status:  MEDLINE    
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.
Lu Deng; Ries J Langley; Patrick H Brown; Gang Xu; Leslie Teng; Qian Wang; Monica I Gonzales; Glenda G Callender; Michael I Nishimura; Suzanne L Topalian; Roy A Mariuzza
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural     Date:  2007-03-04
Journal Detail:
Title:  Nature immunology     Volume:  8     ISSN:  1529-2908     ISO Abbreviation:  Nat. Immunol.     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-03-21     Completed Date:  2007-05-17     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  100941354     Medline TA:  Nat Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  398-408     Citation Subset:  IM    
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MeSH Terms
Amino Acid Sequence
Cell Line, Tumor
Crystallography, X-Ray
Epitopes / immunology
HLA-DR1 Antigen / chemistry,  immunology*
Melanoma / enzymology,  genetics,  immunology*
Models, Molecular
Molecular Sequence Data
Point Mutation / immunology
Protein Conformation
Receptors, Antigen, T-Cell / chemistry,  immunology*
Surface Plasmon Resonance
Triose-Phosphate Isomerase / chemistry,  genetics,  immunology*
Grant Support
Reg. No./Substance:
0/Epitopes; 0/HLA-DR1 Antigen; 0/Receptors, Antigen, T-Cell; EC Isomerase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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