tetano
Editor, Senior Moderator
APMIS
. 2026 Nov;134(11):e70282.
doi: 10.1111/apm.70282.
Jiezuan Yang 1 , Xuehui Zhao 1 2 , Dangsheng Xiao 3 , Hua Zhang 1 , Haifeng Lu 1
Affiliations Expand
Severe H1N1 influenza remains a global health concern, but the immunological mechanisms underlying disease severity are not fully understood. In this study, we used high-throughput sequencing to profile the T cell receptor beta chain (TRB) complementarity-determining region 3 (CDR3) repertoire in 24 H1N1 patients (12 mild, 12 severe) during the 2009 pandemic. Our analysis revealed significant differences in TRB diversity and clonal expansion between severity groups. Severe patients had significantly reduced TRBV11-3 usage and overall TRB diversity, as indicated by lower Shannon entropy and fewer clonotypes. Twelve TRBV-BJ combinations were downregulated, whereas one was upregulated in severe cases. Similarly, 20 V-D-J combinations were significantly less frequent, and two were more prevalent in severe patients. Severe infection was associated with a higher proportion of hyper-expanded clones, indicating an intense oligoclonal T cell response that narrows repertoire diversity. These characteristic CDR3 repertoire changes provide important insights into the immunopathogenesis of severe influenza and may inform the development of new diagnostic approaches and T cell-targeted therapies. Our findings highlight the value of TCR repertoire profiling for stratifying disease severity and guiding future research on emerging influenza viruses, with potential for translating immunological insights into clinical applications.
Keywords: H1N1 influenza; T cell receptor; clinical application; high‐throughput sequencing; immune repertoire.
. 2026 Nov;134(11):e70282.
doi: 10.1111/apm.70282.
Profiling of the T Cell Receptor Repertoire Reveals Different Immunological Signatures Between Mild and Severe H1N1 Infection
Jiezuan Yang 1 , Xuehui Zhao 1 2 , Dangsheng Xiao 3 , Hua Zhang 1 , Haifeng Lu 1
Affiliations Expand
- PMID: 43009144
- DOI: 10.1111/apm.70282
Abstract
Severe H1N1 influenza remains a global health concern, but the immunological mechanisms underlying disease severity are not fully understood. In this study, we used high-throughput sequencing to profile the T cell receptor beta chain (TRB) complementarity-determining region 3 (CDR3) repertoire in 24 H1N1 patients (12 mild, 12 severe) during the 2009 pandemic. Our analysis revealed significant differences in TRB diversity and clonal expansion between severity groups. Severe patients had significantly reduced TRBV11-3 usage and overall TRB diversity, as indicated by lower Shannon entropy and fewer clonotypes. Twelve TRBV-BJ combinations were downregulated, whereas one was upregulated in severe cases. Similarly, 20 V-D-J combinations were significantly less frequent, and two were more prevalent in severe patients. Severe infection was associated with a higher proportion of hyper-expanded clones, indicating an intense oligoclonal T cell response that narrows repertoire diversity. These characteristic CDR3 repertoire changes provide important insights into the immunopathogenesis of severe influenza and may inform the development of new diagnostic approaches and T cell-targeted therapies. Our findings highlight the value of TCR repertoire profiling for stratifying disease severity and guiding future research on emerging influenza viruses, with potential for translating immunological insights into clinical applications.
Keywords: H1N1 influenza; T cell receptor; clinical application; high‐throughput sequencing; immune repertoire.