6C68

MHC-independent t cell receptor A11


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.59 Å
  • R-Value Free: 0.258 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.205 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structure of MHC-Independent TCRs and Their Recognition of Native Antigen CD155.

Lu, J.Van Laethem, F.Saba, I.Chu, J.Tikhonova, A.N.Bhattacharya, A.Singer, A.Sun, P.D.

(2020) J Immunol 204: 3351-3359

  • DOI: https://doi.org/10.4049/jimmunol.1901084
  • Primary Citation of Related Structures:  
    6C61, 6C68

  • PubMed Abstract: 

    During normal T cell development in the thymus, αβ TCRs signal immature thymocytes to differentiate into mature T cells by binding to peptide-MHC ligands together with CD4/CD8 coreceptors. Conversely, in MHC and CD4/CD8 coreceptor-deficient mice, the thymus generates mature T cells expressing MHC-independent TCRs that recognize native conformational epitopes rather than linear antigenic-peptides presented by MHC. To date, no structural information of MHC-independent TCRs is available, and their structural recognition of non-MHC ligand remains unknown. To our knowledge in this study, we determined the first structures of two murine MHC-independent TCRs (A11 and B12A) that bind with high nanomolar affinities to mouse adhesion receptor CD155. Solution binding demonstrated the Vαβ-domain is responsible for MHC-independent B12A recognition of its ligand. Analysis of A11 and B12A sequences against various MHC-restricted and -independent TCR sequence repertoires showed that individual V-genes of A11 and B12A did not exhibit preference against MHC-restriction. Likewise, CDR3 alone did not discriminate against MHC binding, suggesting VDJ recombination together with Vα/Vβ pairing determine their MHC-independent specificity for CD155. The structures of A11 and B12A TCR are nearly identical to those of MHC-restricted TCR, including the conformations of CDR1 and 2. Mutational analysis, together with negative-staining electron microscopy images, showed that the CDR regions of A11 and B12A recognized epitopes on D1 domain of CD155, a region also involved in CD155 binding to poliovirus and Tactile in human. Taken together, MHC-independent TCRs adopt canonical TCR structures to recognize native Ags, highlighting the importance of thymic selection in determining TCR ligand specificity.


  • Organizational Affiliation

    Structural Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Rockville, MD 20852; and.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
T-cell receptor alpha chain
A, C
206Mus musculusMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
T-cell receptor beta chain
B, D
240Mus musculusMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.59 Å
  • R-Value Free: 0.258 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.205 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 89.24α = 90
b = 102.555β = 90
c = 118.503γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
SCALEITdata reduction
HKL-2000data scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2019-01-30
    Type: Initial release
  • Version 1.1: 2020-08-12
    Changes: Database references
  • Version 1.2: 2023-10-04
    Changes: Data collection, Database references, Refinement description