Hepatitis B virus surface antigen drives T cell immunity through non-canonical antigen presentation in mice
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 cel...
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| Format: | Article |
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59985-8 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Xiaofang Li |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-bfdbcd42281c41cbbf57a418b9c9c2dd |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-bfdbcd42281c41cbbf57a418b9c9c2dd2025-08-20T03:53:58ZengNature PortfolioNature Communications2041-17232025-05-0116112010.1038/s41467-025-59985-8Hepatitis B virus surface antigen drives T cell immunity through non-canonical antigen presentation in miceXiaofang Li0Wenxuan Sun1Xiaolan Xu2Qirong Jiang3Yuheng Shi4Huixi Zhang5Weien Yu6Bisheng Shi7Simin Wan8Jiangxia Liu9Wuhui Song10Jiming Zhang11Zhenghong Yuan12Jianhua Li13Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan UniversityKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan UniversityKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan UniversityDepartment of Infectious Diseases, Huashan Hospital, Fudan UniversityKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan UniversityKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan UniversityDepartment of Infectious Diseases, Huashan Hospital, Fudan UniversityKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan UniversityKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan UniversityKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan UniversityKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan UniversityDepartment of Infectious Diseases, Huashan Hospital, Fudan UniversityKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan UniversityKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan UniversityAbstract 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.https://doi.org/10.1038/s41467-025-59985-8 |
| spellingShingle | 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 Hepatitis B virus surface antigen drives T cell immunity through non-canonical antigen presentation in mice Nature Communications |
| title | Hepatitis B virus surface antigen drives T cell immunity through non-canonical antigen presentation in mice |
| title_full | Hepatitis B virus surface antigen drives T cell immunity through non-canonical antigen presentation in mice |
| title_fullStr | Hepatitis B virus surface antigen drives T cell immunity through non-canonical antigen presentation in mice |
| title_full_unstemmed | Hepatitis B virus surface antigen drives T cell immunity through non-canonical antigen presentation in mice |
| title_short | Hepatitis B virus surface antigen drives T cell immunity through non-canonical antigen presentation in mice |
| title_sort | hepatitis b virus surface antigen drives t cell immunity through non canonical antigen presentation in mice |
| url | https://doi.org/10.1038/s41467-025-59985-8 |
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