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Hepatitis B virus surface antigen drives T cell immunity through non-canonical antigen presentation in mice

Author

Listed:
  • Xiaofang Li

    (Fudan University)

  • Wenxuan Sun

    (Fudan University)

  • Xiaolan Xu

    (Fudan University)

  • Qirong Jiang

    (Fudan University)

  • Yuheng Shi

    (Fudan University)

  • Huixi Zhang

    (Fudan University)

  • Weien Yu

    (Fudan University)

  • Bisheng Shi

    (Fudan University)

  • Simin Wan

    (Fudan University)

  • Jiangxia Liu

    (Fudan University)

  • Wuhui Song

    (Fudan University)

  • Jiming Zhang

    (Fudan University)

  • Zhenghong Yuan

    (Fudan University)

  • Jianhua Li

    (Fudan University)

Abstract

Hepatitis B virus (HBV) exclusively infects hepatocytes and produces large amounts of subviral particles containing its surface antigen (HBsAg). T cell immunity is crucial for controlling and clearing HBV infection. However, the intercellular processes underlying HBsAg presentation to T cells are incompletely understood. Here, using preclinical mouse models, we show that, following HBsAg expression, the intrahepatic Batf3+XCR1+CCR7- conventional dendritic cell subset cDC1 presents HBsAg by MHC-I cross-dressing, driving CD8+ T cell response. Meanwhile, upon HBsAg access to lymphoid tissues, B cells acquire HBsAg directly in the follicles of lymphoid tissues and initiate CD4+ T cell responses sequentially in the follicular and interfollicular regions, guided by chemoattractant receptors CCR5 and EBI2, respectively. Finally, we identify ALCAM, LFA-1, and CD80 as key co-stimulatory signals essential for optimal T cell responses. Thus, these findings reveal the roadmap of non-canonical antigen presentation that drives T cell immunity against HBsAg, advancing novel therapeutic strategies for chronic HBV infection.

Suggested Citation

  • Xiaofang Li & Wenxuan Sun & Xiaolan Xu & Qirong Jiang & Yuheng Shi & Huixi Zhang & Weien Yu & Bisheng Shi & Simin Wan & Jiangxia Liu & Wuhui Song & Jiming Zhang & Zhenghong Yuan & Jianhua Li, 2025. "Hepatitis B virus surface antigen drives T cell immunity through non-canonical antigen presentation in mice," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59985-8
    DOI: 10.1038/s41467-025-59985-8
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    References listed on IDEAS

    as
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