tetano
Editor, Senior Moderator
Int Immunol
. 2026 Feb 10:dxag008.
doi: 10.1093/intimm/dxag008. Online ahead of print.
Epitope specificity shapes the CD4+ T cell response to influenza virus infection in mice
Daiki Mori[SUP] 1 [/SUP], Nicolas Sax[SUP] 2 [/SUP], Nozomi Shimada[SUP] 1 [/SUP], Mana Kuwabara[SUP] 1 [/SUP], Isao Ebina[SUP] 3 4 [/SUP], Ryusuke Omiya[SUP] 3 4 [/SUP], Kunihiro Hattori[SUP] 3 4 [/SUP], Ryo Shinnakasu[SUP] 5 [/SUP], Kazuo Yamashita[SUP] 2 [/SUP], Sho Yamasaki[SUP] 6 7 8 9 [/SUP], Tomohiro Kurosaki[SUP] 5 8 10 [/SUP], Wataru Ise[SUP] 1 5 9 [/SUP]
Affiliations
Helper CD4+ T cells play a central role in orchestrating protective immune responses during infection and vaccination. Activation of naïve CD4+ T cells is initiated by the recognition of antigenic peptides presented on MHC class II molecules, leading to their differentiation into distinct effector subsets. In the context of influenza virus infection, the quality of CD4+ T cell reponses is a critical determinant of both cellular and humoral immunity. Given the limited breadth of protection conferred by current influenza vaccines, which primarily induce strain-specific neutralizing antibodies, there is growing interest in harnessing CD4+ T cell responses targeting conserved viral epitopes to achieve broader and more durable protection. Identifying potent T cell epitopes within viral antigens is therefore critical for designing effective vaccines that elicit robust, durable, and cross-protective helper T cell and antibody responses. In this study, using a mouse model of influenza virus infection, we identified CD4+ T cell epitopes within the hemagglutinin (HA) and nucleoprotein (NP) of the H1N1 strain. We generated two NP peptide/MHC class II tetramers, NP264-274/I-Ab and NP418-428/I-Ab, which enabled in vivo tracking and characterization of epitope-specific CD4+ T cells during infection. These epitope-specific T cells exhibited distinct TCR repertoires and differentiation patterns toward either Th1 or T follicular helper (Tfh) lineages, suggesting that epitope specificity shapes the quality of the T cell response. Our findings provide new insights into the epitope-dependent functional diversity of helper T cell responses and offer valuable tools for the rational design of broadly protective influenza vaccines.
Keywords: influenza; peptide/MHC tetramer.
. 2026 Feb 10:dxag008.
doi: 10.1093/intimm/dxag008. Online ahead of print.
Epitope specificity shapes the CD4+ T cell response to influenza virus infection in mice
Daiki Mori[SUP] 1 [/SUP], Nicolas Sax[SUP] 2 [/SUP], Nozomi Shimada[SUP] 1 [/SUP], Mana Kuwabara[SUP] 1 [/SUP], Isao Ebina[SUP] 3 4 [/SUP], Ryusuke Omiya[SUP] 3 4 [/SUP], Kunihiro Hattori[SUP] 3 4 [/SUP], Ryo Shinnakasu[SUP] 5 [/SUP], Kazuo Yamashita[SUP] 2 [/SUP], Sho Yamasaki[SUP] 6 7 8 9 [/SUP], Tomohiro Kurosaki[SUP] 5 8 10 [/SUP], Wataru Ise[SUP] 1 5 9 [/SUP]
Affiliations
- PMID: 41664926
- DOI: 10.1093/intimm/dxag008
Helper CD4+ T cells play a central role in orchestrating protective immune responses during infection and vaccination. Activation of naïve CD4+ T cells is initiated by the recognition of antigenic peptides presented on MHC class II molecules, leading to their differentiation into distinct effector subsets. In the context of influenza virus infection, the quality of CD4+ T cell reponses is a critical determinant of both cellular and humoral immunity. Given the limited breadth of protection conferred by current influenza vaccines, which primarily induce strain-specific neutralizing antibodies, there is growing interest in harnessing CD4+ T cell responses targeting conserved viral epitopes to achieve broader and more durable protection. Identifying potent T cell epitopes within viral antigens is therefore critical for designing effective vaccines that elicit robust, durable, and cross-protective helper T cell and antibody responses. In this study, using a mouse model of influenza virus infection, we identified CD4+ T cell epitopes within the hemagglutinin (HA) and nucleoprotein (NP) of the H1N1 strain. We generated two NP peptide/MHC class II tetramers, NP264-274/I-Ab and NP418-428/I-Ab, which enabled in vivo tracking and characterization of epitope-specific CD4+ T cells during infection. These epitope-specific T cells exhibited distinct TCR repertoires and differentiation patterns toward either Th1 or T follicular helper (Tfh) lineages, suggesting that epitope specificity shapes the quality of the T cell response. Our findings provide new insights into the epitope-dependent functional diversity of helper T cell responses and offer valuable tools for the rational design of broadly protective influenza vaccines.
Keywords: influenza; peptide/MHC tetramer.