9XME

Complex of HLA-A2, a class I MHC, with a wild type UTP20 peptide

Summary for 9XME

• Entry DOI: 10.2210/pdb9xme/pdb
• Descriptor: MHC class I antigen, Beta-2-microglobulin, Small subunit processome component 20 homolog, ... (4 entities in total)
• Functional Keywords: complex of hla-a2, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 89653.79

Authors

Wang, J.,Wu, D.C. (deposition date: 2025-11-10, release date: 2026-09-23, Last modification date: 2026-09-30)

Primary citation

Wang, J.,Li, S.,Mao, L.,Yang, D.,Yao, Z.,Shi, J.,He, W.,Wu, D.
Structural basis for CD8 + T cell recognition of the charge-reversed neoantigen UTP20 D2661H .
J.Struct.Biol., 218:108371-108371, 2026

PubMed Abstract: Adoptive T cell therapy (ACT) eliminates tumors by infusing tumor reactive T cells. Neoantigens from somatic mutations are ideal targets due to their absence in normal tissues. How charge-reversing mutations drive neoantigen immunogenicity remains unclear. Here, we determined the wild-type and mutant UTP20-HLA-A2 structures and found them nearly identical except at the mutation site (Asp to His). The TCR-pHLA structure revealed selective recognition through specific interactions between CDR loops and the mutation site. Rosetta calculations showed that His provides favorable interactions absent in the wild-type. TCR engagement also induced a flip of the P6 side chain, reshaping the interface. These findings provide a structural basis for charge-reversed mutation-driven T cell responses and inform neoantigen-based ACT development.

PubMed: 42727733
DOI: 10.1016/j.jsb.2026.108371

Experimental method

X-RAY DIFFRACTION (2.04 Å)