6C61

MHC-independent T-cell receptor B12A

Summary for 6C61

• Entry DOI: 10.2210/pdb6c61/pdb
• Descriptor: T-cell receptor alpha chain, T-cell receptor beta chain (3 entities in total)
• Functional Keywords: mhc-independent t cell receptor, immune system
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 2
• Total formula weight: 50412.18

Authors

Lu, J.,Sun, P. (deposition date: 2018-01-17, release date: 2019-01-30, Last modification date: 2024-11-13)

Primary citation

Lu, J.,Van Laethem, F.,Saba, I.,Chu, J.,Tikhonova, A.N.,Bhattacharya, A.,Singer, A.,Sun, P.D.
Structure of MHC-Independent TCRs and Their Recognition of Native Antigen CD155.
J Immunol., 204:3351-3359, 2020

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.

PubMed: 32321756
DOI: 10.4049/jimmunol.1901084

Experimental method

X-RAY DIFFRACTION (2.43 Å)