Soluble transferrin mediates targeting of hepatitis B envelope antigen to transferrin receptor and its presentation by activated T cells.
In a previous study, we identified that transferrin receptor (TfR) is the receptor utilized by hepatitis B virus (HBV) to enter T cells. We demonstrated that hepatitis B envelope antigen (HBenvAg) is taken up by activated T cells via TfR, processed in endosomal compartments, and presented on class II molecules to specific CD4+ T cell clones. Herein, we report that binding to soluble ferric Tf by HBenvAg is needed in TfR-mediated endocytosis. Accordingly, presentation of HBenvAg by activated T cells is not observed in serum-free medium and is restored by addition of soluble Tf. Moreover, we provide evidence that pre-S2 and S regions of HBenvAg contain the critical residues for the interaction with soluble Tf. Our data not only explain HBV entry into a variety of host activated cells, but may also help in developing strategies to alter the course of chronic HBV infection.
Gagliardi
M C
MC
Istituto I Clinica Medica, University of Rome La Sapienza, Italy.
Nisini
R
R
Benvenuto
R
R
De Petrillo
G
G
Michel
M L
ML
Barnaba
V
V
D017951:Antigen Presentation / Q000502:physiology; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004797:Enzyme-Linked Immunosorbent Assay; D006514:Hepatitis B Surface Antigens / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D011990:Receptors, Transferrin / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014168:Transferrin / Q000502:physiology*; D014759:Viral Envelope Proteins / Q000276:immunology* / Q000378:metabolism
D016895:Culture Media, Serum-Free; D006514:Hepatitis B Surface Antigens; D011990:Receptors, Transferrin; D014168:Transferrin; D014759:Viral Envelope Proteins