SARS-CoV-2 mutations affect antigen processing by the proteasome to alter CD8+ T cell responses

Autor: Dannielle Wellington, Zixi Yin, Zhanru Yu, Raphael Heilig, Simon Davis, Roman Fischer, Suet Ling Felce, Elie Antoun, Philip Hublitz, Ryan Beveridge, Danning Dong, Guihai Liu, Xuan Yao, Yanchun Peng, Benedikt M. Kessler, Tao Dong
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Heliyon, Vol 9, Iss 10, Pp e20076- (2023)
Druh dokumentu: article
ISSN: 2405-8440
DOI: 10.1016/j.heliyon.2023.e20076
Popis: Mutations within viral epitopes can result in escape from T cells, but the contribution of mutations in flanking regions of epitopes in SARS-CoV-2 has not been investigated. Focusing on two SARS-CoV-2 nucleoprotein CD8+ epitopes, we investigated the contribution of these flanking mutations to proteasomal processing and T cell activation. We found decreased NP9-17-B*27:05 CD8+ T cell responses to the NP-Q7K mutation, likely due to a lack of efficient epitope production by the proteasome, suggesting immune escape caused by this mutation. In contrast, NP-P6L and NP-D103 N/Y mutations flanking the NP9-17-B*27:05 and NP105-113-B*07:02 epitopes, respectively, increased CD8+ T cell responses associated with enhanced epitope production by the proteasome. Our results provide evidence that SARS-CoV-2 mutations outside the epitope could have a significant impact on proteasomal processing, either contributing to T cell escape or enhancement that may be exploited for future vaccine design.
Databáze: Directory of Open Access Journals