8ESA

CryoEM structure of HLA-A2 bound to MAGEA4 (230-239) peptide

Summary for 8ESA

• Entry DOI: 10.2210/pdb8esa/pdb
• EMDB information: 28570 28571 28572 28573 28574
• Descriptor: Beta-2-microglobulin,HLA class I antigen,MAGE-A4 peptide chimera (1 entity in total)
• Functional Keywords: hla, mhc, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 150918.55

Authors

Saotome, K.,Franklin, M.C. (deposition date: 2022-10-13, release date: 2023-05-03, Last modification date: 2024-10-23)

Primary citation

Saotome, K.,Dudgeon, D.,Colotti, K.,Moore, M.J.,Jones, J.,Zhou, Y.,Rafique, A.,Yancopoulos, G.D.,Murphy, A.J.,Lin, J.C.,Olson, W.C.,Franklin, M.C.
Structural analysis of cancer-relevant TCR-CD3 and peptide-MHC complexes by cryoEM.
Nat Commun, 14:2401-2401, 2023

PubMed 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.

PubMed: 37100770
DOI: 10.1038/s41467-023-37532-7

Experimental method

ELECTRON MICROSCOPY (3.4 Å)