Structural analysis of cancer-relevant TCR-CD3 and peptide-MHC complexes by cryoEM

Kei Saotome (), Drew Dudgeon, Kiersten Colotti, Michael J. Moore, Jennifer Jones, Yi Zhou, Ashique Rafique, George D. Yancopoulos, Andrew J. Murphy, John C. Lin, William C. Olson and Matthew C. Franklin ()
Additional contact information
Kei Saotome: Regeneron Pharmaceuticals, Inc.
Drew Dudgeon: Regeneron Pharmaceuticals, Inc.
Kiersten Colotti: Regeneron Pharmaceuticals, Inc.
Michael J. Moore: Regeneron Pharmaceuticals, Inc.
Jennifer Jones: Regeneron Pharmaceuticals, Inc.
Yi Zhou: Regeneron Pharmaceuticals, Inc.
Ashique Rafique: Regeneron Pharmaceuticals, Inc.
George D. Yancopoulos: Regeneron Pharmaceuticals, Inc.
Andrew J. Murphy: Regeneron Pharmaceuticals, Inc.
John C. Lin: Regeneron Pharmaceuticals, Inc.
William C. Olson: Regeneron Pharmaceuticals, Inc.
Matthew C. Franklin: Regeneron Pharmaceuticals, Inc.

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: 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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-023-37532-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37532-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-37532-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().