Structural insights into clonal restriction and diversity in T cell recognition of two immunodominant SARS-CoV-2 nucleocapsid epitopes.

ABSTRACT: T cells play a crucial role in clearing SARS-CoV-2 and in forming long-term memory responses to that coronavirus. The highly immunogenic nucleocapsid (N) protein of SARS-CoV-2 is much more conserved than the spike (S) protein across variants of concern, making it an attractive vaccine target for activating cytotoxic CD8⁺ T cells. Of particular interest are the immunodominant N epitopes LLL and SPR. Whereas LLL elicits a clonally restricted T cell response, the response to SPR is highly diverse. To understand the basis for this difference, here we determine structures of T cell receptors (TCRs) bound to LLL-HLA-A2 and SPR-HLA-B7, revealing the structural underpinnings of highly restricted Vα gene usage by LLL-specific TCRs, as well as multiple structural solutions to recognizing

SUBMITTER: Yuan P 

PROVIDER: S-EPMC12749039 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature