biostudies-literatureWellington DMedical Research Councile20076https://www.ebi.ac.uk/biostudies/studies/S-EPMC10570596biostudies-literatureUnknown9(10)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 NP_9-17-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 NP_9-17-B*27:05 and NP_105-113-B*07:02 epitopes, respectively, increased CD8⁺ T cell responses associated with enhanced epitope productHeliyonSARS-CoV-2 mutations affect antigen processing by the proteasome to alter CD8<sup>+</sup> T cell responses.PMC10570596G0501068Peng YDong TFischer RDavis SHeilig RKessler BMYao XYin ZDong DWellington DAntoun EYu ZHublitz PBeveridge RFelce SLLiu GfalseSARS-CoV-2 mutations affect antigen processing by the proteasome to alter CD8<sup>+</sup> T cell responses.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 NP_9-17-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 NP_9-17-B*27:05 and NP_105-113-B*07:02 epitopes, respectively, increased CD8⁺ T cell responses associated with enhanced epitope product2023-01-01T00:00:00Z2023 Oct2026-05-29T06:11:54.366Z2025-04-06T01:59:41.242ZS-EPMC105705963784261910.1016/j.heliyon.2023.e20076