tetano
Editor, Senior Moderator
Nat Immunol
. 2025 Jan 28.
doi: 10.1038/s41590-024-02051-0. Online ahead of print. T cell immune evasion by SARS-CoV-2 JN.1 escapees targeting two cytotoxic T cell epitope hotspots
Jinmin Tian[SUP] #[/SUP][SUP] 1 2 [/SUP], Bingli Shang[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Jianing Zhang[SUP] #[/SUP][SUP] 1 2 [/SUP], Yuanyuan Guo[SUP] #[/SUP][SUP] 1 2 4 [/SUP], Min Li[SUP] #[/SUP][SUP] 1 2 [/SUP], Yuechao Hu[SUP] #[/SUP][SUP] 1 2 [/SUP], Dan Bai[SUP] 1 5 [/SUP], Junying She[SUP] 1 2 3 [/SUP], Yang Han[SUP] 1 2 5 [/SUP], Peipei Guo[SUP] 1 2 4 [/SUP], Mengkun Huang[SUP] 1 2 6 [/SUP], Yalan Wang[SUP] 1 2 [/SUP], Maoshun Liu[SUP] 1 2 [/SUP], Jie Zhang[SUP] 7 8 [/SUP], Beiwei Ye[SUP] 1 2 [/SUP], Yaxin Guo[SUP] 1 2 [/SUP], Mengjie Yang[SUP] 1 2 3 [/SUP], Ying Lin[SUP] 1 4 [/SUP], Ting Zhang[SUP] 1 2 6 [/SUP], Xin Sun[SUP] 1 2 4 [/SUP], Xiaoju Yuan[SUP] 1 2 [/SUP], Danni Zhang[SUP] 1 2 [/SUP], Ziqian Xu[SUP] 1 2 9 [/SUP], Yan Chai[SUP] 10 [/SUP], Jianxun Qi[SUP] 10 [/SUP], Kefang Liu[SUP] 10 [/SUP], Shuguang Tan[SUP] 10 [/SUP], Yingze Zhao[SUP] 11 12 13 [/SUP], Jikun Zhou[SUP] 14 [/SUP], Rui Song[SUP] 15 [/SUP], George F Gao[SUP] 16 17 18 19 20 [/SUP], Jun Liu[SUP] 21 22 23 24 [/SUP]
Affiliations
Although antibody escape is observed in emerging severe acute respiratory syndrome coronavirus 2 variants, T cell escape, especially after the global circulation of BA.2.86/JN.1, is unexplored. Here we demonstrate that T cell evasion exists in epitope hotspots spanning BA.2.86/JN.1 mutations. The newly emerging Q229K at this conserved nucleocapsid protein site impairs HLA-A2 epitope hotspot recognition. The association between HLA-A24 convalescents and T cell immune escape points to the spike (S) protein epitope S[SUB]448-456[/SUB]NYNYLYRLF, with multiple mutations from Delta to JN.1, including L452Q, L452R, F456L, N450D and L452W, and N450D, L452W and L455S. A cliff drop of immune responses was observed for S[SUB]448-456[/SUB]NYNYRYRLF (Delta/BA.5.2) and S[SUB]448-456[/SUB]NYDYWYRSF (JN.1), but with immune preservation of S[SUB]448-456[/SUB]NYDYWYRLF (BA.2.86). Structural analyses showed that hydrophobicity exposure determines the pronounced escape of L452R and L455S mutants, which was further confirmed by T cell receptor binding. This study highlights the characteristics and molecular mechanisms of the T cell immune escape for JN.1 and provides new insights into understanding the dominant circulation of variants, from the viewpoint of cytotoxic T cell evasion.
. 2025 Jan 28.
doi: 10.1038/s41590-024-02051-0. Online ahead of print. T cell immune evasion by SARS-CoV-2 JN.1 escapees targeting two cytotoxic T cell epitope hotspots
Jinmin Tian[SUP] #[/SUP][SUP] 1 2 [/SUP], Bingli Shang[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Jianing Zhang[SUP] #[/SUP][SUP] 1 2 [/SUP], Yuanyuan Guo[SUP] #[/SUP][SUP] 1 2 4 [/SUP], Min Li[SUP] #[/SUP][SUP] 1 2 [/SUP], Yuechao Hu[SUP] #[/SUP][SUP] 1 2 [/SUP], Dan Bai[SUP] 1 5 [/SUP], Junying She[SUP] 1 2 3 [/SUP], Yang Han[SUP] 1 2 5 [/SUP], Peipei Guo[SUP] 1 2 4 [/SUP], Mengkun Huang[SUP] 1 2 6 [/SUP], Yalan Wang[SUP] 1 2 [/SUP], Maoshun Liu[SUP] 1 2 [/SUP], Jie Zhang[SUP] 7 8 [/SUP], Beiwei Ye[SUP] 1 2 [/SUP], Yaxin Guo[SUP] 1 2 [/SUP], Mengjie Yang[SUP] 1 2 3 [/SUP], Ying Lin[SUP] 1 4 [/SUP], Ting Zhang[SUP] 1 2 6 [/SUP], Xin Sun[SUP] 1 2 4 [/SUP], Xiaoju Yuan[SUP] 1 2 [/SUP], Danni Zhang[SUP] 1 2 [/SUP], Ziqian Xu[SUP] 1 2 9 [/SUP], Yan Chai[SUP] 10 [/SUP], Jianxun Qi[SUP] 10 [/SUP], Kefang Liu[SUP] 10 [/SUP], Shuguang Tan[SUP] 10 [/SUP], Yingze Zhao[SUP] 11 12 13 [/SUP], Jikun Zhou[SUP] 14 [/SUP], Rui Song[SUP] 15 [/SUP], George F Gao[SUP] 16 17 18 19 20 [/SUP], Jun Liu[SUP] 21 22 23 24 [/SUP]
Affiliations
- PMID: 39875585
- DOI: 10.1038/s41590-024-02051-0
Although antibody escape is observed in emerging severe acute respiratory syndrome coronavirus 2 variants, T cell escape, especially after the global circulation of BA.2.86/JN.1, is unexplored. Here we demonstrate that T cell evasion exists in epitope hotspots spanning BA.2.86/JN.1 mutations. The newly emerging Q229K at this conserved nucleocapsid protein site impairs HLA-A2 epitope hotspot recognition. The association between HLA-A24 convalescents and T cell immune escape points to the spike (S) protein epitope S[SUB]448-456[/SUB]NYNYLYRLF, with multiple mutations from Delta to JN.1, including L452Q, L452R, F456L, N450D and L452W, and N450D, L452W and L455S. A cliff drop of immune responses was observed for S[SUB]448-456[/SUB]NYNYRYRLF (Delta/BA.5.2) and S[SUB]448-456[/SUB]NYDYWYRSF (JN.1), but with immune preservation of S[SUB]448-456[/SUB]NYDYWYRLF (BA.2.86). Structural analyses showed that hydrophobicity exposure determines the pronounced escape of L452R and L455S mutants, which was further confirmed by T cell receptor binding. This study highlights the characteristics and molecular mechanisms of the T cell immune escape for JN.1 and provides new insights into understanding the dominant circulation of variants, from the viewpoint of cytotoxic T cell evasion.