Distinct epitope-specific memory kinetics within influenza B nucleoprotein shape long-term CD8+ T cell differentiation in the lung
Abstract
CD8+ T cell memory inflation, originally described during murine cytomegalovirus infection, is characterized by the progressive accumulation of antigen-specific memory T cells that retain effector-like features rather than undergoing gradual contraction. Here, using intranasal immunization of CB6F1 mice with a recombinant adenoviral vector expressing influenza B nucleoprotein (NP), we identified two immunodominant epitopes within a single antigen. Whereas Db/BNP352-specific CD8+ T cells dominated during the effector phase, Dd/BNP166-specific cells progressively increased during late memory, consistent with memory inflation. During the effector phase, Dd/BNP166-specific CD8+ T cells exhibited higher inhibitory receptor expression and reduced antigen sensitivity compared with Db/BNP352-specific cells, indicating a regulated effector state. Notably, however, these cells showed greater enrichment of cell-cycle-associated programs and enhanced proliferative capacity. By the memory phase, Dd/BNP166-specific cells displayed increased expression of tissue-resident memory T cell (TRM)-associated markers and higher functional avidity than at earlier time points. Together, these findings reveal divergence in CD8+ T cell memory trajectories between two peptide-MHC-specific populations after intranasal influenza B vaccination and indicate an association between a distinct early effector phenotype, subsequent memory inflation, and the persistence of lung TRM-like CD8+ T cells.
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BibTeX
@article{lee2026distinct,
title = {{Distinct epitope-specific memory kinetics within influenza B nucleoprotein shape long-term CD8+ T cell differentiation in the lung}},
author = {Serin Lee and Eun-Ah Kim and Sun Shim Choi and Jun Chang},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1943778},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1943778},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Distinct epitope-specific memory kinetics within influenza B nucleoprotein shape long-term CD8+ T cell differentiation in the lung
AU - Serin Lee
AU - Eun-Ah Kim
AU - Sun Shim Choi
AU - Jun Chang
PY - 2026
DA - 2026/11/09
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1943778
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1943778
AB - CD8+ T cell memory inflation, originally described during murine cytomegalovirus infection, is characterized by the progressive accumulation of antigen-specific memory T cells that retain effector-like features rather than undergoing gradual contraction. Here, using intranasal immunization of CB6F1 mice with a recombinant adenoviral vector expressing influenza B nucleoprotein (NP), we identified two immunodominant epitopes within a single antigen. Whereas Db/BNP352-specific CD8+ T cells dominated during the effector phase, Dd/BNP166-specific cells progressively increased during late memory, consistent with memory inflation. During the effector phase, Dd/BNP166-specific CD8+ T cells exhibited higher inhibitory receptor expression and reduced antigen sensitivity compared with Db/BNP352-specific cells, indicating a regulated effector state. Notably, however, these cells showed greater enrichment of cell-cycle-associated programs and enhanced proliferative capacity. By the memory phase, Dd/BNP166-specific cells displayed increased expression of tissue-resident memory T cell (TRM)-associated markers and higher functional avidity than at earlier time points. Together, these findings reveal divergence in CD8+ T cell memory trajectories between two peptide-MHC-specific populations after intranasal influenza B vaccination and indicate an association between a distinct early effector phenotype, subsequent memory inflation, and the persistence of lung TRM-like CD8+ T cells.
SN - 1664-3224
ER -