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

Résumé fourni par la source

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. The mechanism of HBsAg antigen presentation to T cells during liver HBV infection is incompletely understood. Here, the authors show that in mice, intrahepatic type I dendritic cells acquire HBsAg by MHC-I complexes through cross-dressing for CD8+ T cell priming, whereas CD4+ T cell responses rely on MHC-II-dependent antigen presentation by B cells in secondary lymphoid tissues.

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