Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human activated T lymphocytes expressing class II molecules are able to present only complex antigens that bind to their own surface receptors, and thus can be captured, internalized, and processed through the class II major histocompatibility complex processing pathway. We have used the antigen-presenting T cell system to identify the viral receptor used by hepatitis B virus (HBV) to enter cells, as well as the sequence of HB envelope antigen (HBenvAg) involved in this interaction. Results show that both CD4+ and CD8+ T clones can process and present HBenvAg to class II-restricted cytotoxic T lymphocytes and that the CD71 transferrin receptor (TfR) is involved in efficient HBenvAg uptake by T cells. Moreover, we provide evidence that the HBenvAg sequence interacting with the T cell surface is contained within the pre-S2 region. Since TfR is also expressed on hepatocytes, it might represent a portal of cellular entry for HBV infection. This system of antigen presentation by T cells may serve as a model to study both lymphocyte receptors used by lymphocytotropic viruses and viral proteins critical to bind them.
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PMID:Transferrin receptor mediates uptake and presentation of hepatitis B envelope antigen by T lymphocytes. 156 93

Synaptophysin is a major transmembrane glycoprotein of a type of small vesicle with an electron-translucent content (SET vesicles), including the approximately 50-nm presynaptic vesicles in neuronal cells, and of similar, somewhat larger (< or = approximately 90 nm) vesicles (SLMV) in neuroendocrine (NE) cells. When certain epithelial non-NE cells, such as human hepatocellular carcinoma PLC cells, were cDNA transfected to synthesize synaptophysin, the new molecules appeared in specific SET vesicles. As this was in contrast to other reports that only NE cells were able to sort synaptophysin away from other plasma membrane proteins into presynaptic- or SLMV-type vesicles, we have further characterized the vesicles containing synaptophysin in transfected PLC cells. Using fractionation and immunoisolation techniques, we have separated different kinds of vesicles, and we have identified a distinct type of synaptophysin-rich, small (30-90-nm) vesicle that contains little, if any, protein of the constitutive secretory pathway marker hepatitis B surface antigen, of the fluid phase endocytosis marker HRP, and of the plasma membrane recycling endosomal marker transferrin receptor. In addition, we have found variously sized vesicles that contained both synaptophysin and transferrin receptor. A corresponding result was also obtained by direct visualization, using double-label immunofluorescence microscopy for the endocytotic markers and synaptophysin in confocal laser scan microscopy and in double-immunogold label electron microscopy. We conclude that diverse non-NE cells of epithelial nature are able to enrich the "foreign" molecule synaptophysin in a category of SET vesicles that are morphologically indistinguishable from SLMV of NE cells, including one type of vesicle in which synaptophysin is sorted away from endosomal marker proteins. Possible mechanisms of this sorting are discussed.
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PMID:Sorting of synaptophysin into special vesicles in nonneuroendocrine epithelial cells. 779 14

Receptor-mediated uptake increases by several orders of magnitude the efficiency of APC to internalize Ag, and is stringently required for the Ag-presenting function of T lymphocytes due to their inability to take up Ag non-specifically. We have previously reported that hepatitis B envelope antigen (HBenvAg) can be internalized by T cells via transferrin receptor (TfR). To evaluate if Ag targeting to receptors expressed on APC could be an effective tool for promoting Ag uptake and presentation, we tested the capacity of activated T cells not expressing TfR to induce HBenvAg-specific T-cell responses when pulsed with a hybrid particle containing HBenvAg coupled to gp120 of human immunodeficiency virus (HIV), exploiting the ability of gp120 to bind to CD4 receptor. We found that CD4+/TfR- T cells pulsed either with the hybrid particle or peptide (S193-207) but not with S, L Ag, a recombinant form of HBenvAg, induced a specific proliferative response of a T-cell clone recognizing peptide (S193-207) of HBenvAg. The finding that the addition of anti-CD4 monoclonal antibody (mAb) before the pulsing of CD4+/TfR- T cells with the hybrid particle drastically blocked the specific T-cell response, together with the finding that CD8+/TfR- T cells were unable to serve as APC even if pulsed with this molecule, demonstrated that CD4 receptor was crucial for the HBenvAg internalization. On the other hand, HBenvAg presentation by CD4+/TfR+ T cells pulsed with the hybrid particle was inhibited only when both anti-CD4 and anti-TfR were added before the pulsing. These results suggest that Ag targeting to APC receptors may be usefully exploited to improve Ag-presentation efficiency in potential immunotherapeutic approaches.
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PMID:Antigen targeting to antigen-presenting cells enhances presentation to class II-restricted T lymphocytes. 790 75

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.
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PMID:Soluble transferrin mediates targeting of hepatitis B envelope antigen to transferrin receptor and its presentation by activated T cells. 820 97

Hepatitis B virus X protein (HBx) is involved in viral metabolism and progression of liver disease. Iron metabolism plays a significant role in liver disease. In this report, to elucidate the relationship between iron metabolism and HBx, we established the Huh7 cell lines in which HBx was stably expressed (Huh7-HBx). In Huh7-HBx, we observed that transferrin receptor 1 (TfR1) expression decreased and ferritin heavy chain (FtH) expression increased as well as reactive oxygen species (ROS) level increased. We also found that these modulations were caused by the downregulation of iron regulatory protein 1 (IRP1). Furthermore, the levels of total iron and labile iron pool (LIP) were altered in Huh7-HBx. In addition, antioxidant N-acetylcystein (NaC) increased IRP1 expression by depleting HBx-induced ROS. We also confirmed these alterations of TfR1 and FtH in the primary hepatocytes of HBx transgenic mice and in HepG2.2.15 cells that constitutively replicate the intact HBV genome. In conclusion, these results suggest that HBx modulates iron metabolism via ROS leading to pathological status in liver diseases.
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PMID:HBx modulates iron regulatory protein 1-mediated iron metabolism via reactive oxygen species. 1826 2