Artikel ; Online: Structural analysis of cancer-relevant TCR-CD3 and peptide-MHC complexes by cryoEM.
2023 Band 14, Heft 1, Seite(n) 2401
Abstract: The recognition of antigenic peptide-MHC (pMHC) molecules by T-cell receptors (TCR) initiates the T-cell mediated immune response. Structural characterization is key for understanding the specificity of TCR-pMHC interactions and informing the development ...
| Abstract | The recognition of antigenic peptide-MHC (pMHC) molecules by T-cell receptors (TCR) initiates the T-cell mediated immune response. Structural characterization is key for understanding the specificity of TCR-pMHC interactions and informing the development of therapeutics. Despite the rapid rise of single particle cryoelectron microscopy (cryoEM), x-ray crystallography has remained the preferred method for structure determination of TCR-pMHC complexes. Here, we report cryoEM structures of two distinct full-length α/β TCR-CD3 complexes bound to their pMHC ligand, the cancer-testis antigen HLA-A2/MAGEA4 (230-239). We also determined cryoEM structures of pMHCs containing MAGEA4 (230-239) peptide and the closely related MAGEA8 (232-241) peptide in the absence of TCR, which provided a structural explanation for the MAGEA4 preference displayed by the TCRs. These findings provide insights into the TCR recognition of a clinically relevant cancer antigen and demonstrate the utility of cryoEM for high-resolution structural analysis of TCR-pMHC interactions. |
|---|---|
| Mesh-Begriff(e) | Humans ; Cryoelectron Microscopy ; Protein Binding ; Receptors, Antigen, T-Cell/metabolism ; Peptides/chemistry ; Histocompatibility Antigens/metabolism ; Neoplasms ; Major Histocompatibility Complex |
| Chemische Substanzen | Receptors, Antigen, T-Cell ; Peptides ; Histocompatibility Antigens |
| Sprache | Englisch |
| Erscheinungsdatum | 2023-04-26 |
| Erscheinungsland | England |
| Dokumenttyp | Journal Article |
| ZDB-ID | 2553671-0 |
| ISSN | 2041-1723 ; 2041-1723 |
| ISSN (online) | 2041-1723 |
| ISSN | 2041-1723 |
| DOI | 10.1038/s41467-023-37532-7 |
| Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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