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In this study, we aimed to assess CD8+ T cell responses following a third dose of the Pfizer BNT162b2 COVID-19 vaccine and identify factors contributing to their longevity. Using HLA tetramers, we analyzed antigen-specific CD8+ T cells in 141 vaccinated individuals (86.5% female) and identified 2 groups: those with strong responses (strong group) and those with weak responses (weak group) 6 mo after the third mRNA vaccination. Transcriptomic analysis revealed that Notch signaling was upregulated in the strong group, and in vitro, the inhibition of Notch signaling significantly reduced CD8+ T cell expansion. These findings suggest that Notch signaling may contribute to maintain long-term antigen-specific CD8+ T cell responses following mRNA vaccination. Targeting this pathway could offer novel strategies for enhancing vaccine-induced cellular immunity and long-lasting protection.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag074","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T13:10:49Z","timestamp":1780924249000},"source":"Crossref","is-referenced-by-count":0,"title":["Sustained antigen-specific CD8+ T cell immunity post\u2013mRNA booster requires notch pathway activation"],"prefix":"10.1093","volume":"215","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6011-9631","authenticated-orcid":false,"given":"Takuto","family":"Nogimori","sequence":"first","affiliation":[{"name":"Laboratory of Precision Immunology, Center for Intractable Diseases and ImmunoGenomics, National Institutes of Biomedical Innovation, Health, and Nutrition , Osaka,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinori","family":"Okina","sequence":"additional","affiliation":[{"name":"Laboratory 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