9F13

Crystal structure of HLA-C*12:02 in complex with KAYNVTQAF (KF9), a 9-mer epitope from SARS-CoV-2 Nucleocapsid (N266-274)

Summary for 9F13

• Entry DOI: 10.2210/pdb9f13/pdb
• Descriptor: HLA class I histocompatibility antigen C alpha chain, Beta-2-microglobulin, Nucleoprotein, ... (4 entities in total)
• Functional Keywords: human leukocyte antigen, major histocompatibility complex, hla-c12, hla-c*12:02, sars-cov-2, nucleocapsid, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 53857.20

Authors

Ahn, Y.M.,Maddumage, J.C.,Chatzileontiadou, D.S.M.,Gras, S. (deposition date: 2024-04-18, release date: 2025-08-06, Last modification date: 2025-09-10)

Primary citation

Goto, Y.,Ahn, Y.M.,Toyoda, M.,Hamana, H.,Jin, Y.,Aritsu, Y.,Nakama, T.,Tajima, Y.,Maddumage, J.C.,Li, H.,Kitamatsu, M.,Kishi, H.,Yonekawa, A.,Jayasinghe, D.,Shimono, N.,Nagasaki, Y.,Minami, R.,Toya, T.,Sekiya, N.,Tomita, Y.,Chatzileontiadou, D.S.M.,Nakata, H.,Nakagawa, S.,Sakagami, T.,Ueno, T.,Gras, S.,Motozono, C.
Molecular basis of potent antiviral HLA-C-restricted CD8 + T cell response to an immunodominant SARS-CoV-2 nucleocapsid epitope.
Nat Commun, 16:8062-8062, 2025

PubMed Abstract: The emergence of SARS-CoV-2 Variants of Concern (VOC) is a major clinical threat; however, VOC remain susceptible to cytotoxic T lymphocyte (CTL) recognition. Therefore, it is crucial to identify potent CTL responses targeting conserved epitopes across VOCs. Here, we demonstrate that the nucleocapsid (N) protein induces efficient CTL responses in early pandemic COVID-19 convalescent donors. In the context of the HLA-A24-B52-C12 haplotype, prevalent in Japan, the KF9 peptide (N: KAYNVTQAF) is immunodominant and restricted by HLA-C*12:02. KF9-specific T cells are cytotoxic and suppress viral replication of both the ancestral and multiple VOC SARS-CoV-2. KF9-specific CD8 T cells maintain effector memory and terminally differentiated phenotypes for 12 months post-infection and proliferate rapidly upon recall. We also determine the structure of a TCR in the context of the HLA-C*12:02-KF9 complex, providing a prototype for the interaction of HLA-C with viral peptides. Surprisingly, despite the TCR's high affinity, the CDR3β loop almost lacks contact with the KF9 peptide. These findings highlight the importance of conserved epitopes and the role of HLA-C molecules in controlling SARS-CoV-2 VOC.

PubMed: 40877317
DOI: 10.1038/s41467-025-63288-3

Experimental method

X-RAY DIFFRACTION (1.61 Å)