Mary Wilson
Well-known member
Published: 28 January 2025
https://doi.org/10.1038/s41590-024-02051-0
Tian, J., Shang, B., Zhang, J. et al.
Abstract
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.
https://www.nature.com/articles/s41590-024-02051-0#citeas
https://doi.org/10.1038/s41590-024-02051-0
Tian, J., Shang, B., Zhang, J. et al.
Abstract
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.
https://www.nature.com/articles/s41590-024-02051-0#citeas