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...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-05-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59985-8 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | 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. |
|---|---|
| ISSN: | 2041-1723 |