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Cross-linking of Fas By Antibodies to a Peculiar Domain of gp120 V3 Loop Can Enhance T Cell Apoptosis in HIV-1–infected Patients
| Content Provider | Scilit |
|---|---|
| Author | Silvestris, Franco Nagata, Shigekazu Cafforio, Paola Silvestris, Nicola Dammacco, Franco |
| Copyright Year | 1996 |
| Description | Previous studies have demonstrated that T cell–reactive antibodies in HIV-1 infection contribute to lymphocyte depletion by cytotoxicity that involves differential membrane targets, such as the 43.5-kD receptor on CEM cells. Here, we show that these antibodies bind Fas as result of a molecular mimicry of the gp120. Both flow cytometry and immunoblotting using the human Fas-transfected mouse WC8 lymphoma revealed positive binding of immunoglobulin G from several patients to a 43.8-kD membrane receptor that also reacts with the CH11 anti-Fas monoclonal antibody. Specificity to Fas was further confirmed to chimeric recombinant human Fas-Fc by ELISA, whereas overlapping peptide mapping of a Fas domain (VEINCTR–N) shared by gp120 V3 loop demonstrated a predominant affinity to the full-length 10-mer peptide. Four anti-Fas affinity preparations greatly increased the subdiploid DNA peak of CEM cells similar to agonist ligands of Fas. In addition, anti-Fas immunoglobulin G strongly inhibited the [3H]thymidine uptake of CEM cells in proliferative assays, inducing a suppression as high as provoked by both CH11 mAb and recombinant human Fas ligand. Since anti-Fas were reactive to gp120, it is conceivable that antibodies binding that domain within the V3 region are effective cross-linkers of Fas and increase apoptosis in peripheral T cells. These results suggest that autologous stimulation of the Fas pathway, rather than of lymphocytotoxic antibodies, may aggravate lymphopenia in a number of HIV-1+ subjects. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196362/pdf http://jem.rupress.org/content/184/6/2287.full.pdf |
| Ending Page | 2300 |
| Page Count | 14 |
| Starting Page | 2287 |
| DOI | 10.1084/jem.184.6.2287 |
| Journal | The Journal of experimental medicine |
| Issue Number | 6 |
| Volume Number | 184 |
| Language | English |
| Publisher | Rockefeller University Press |
| Publisher Date | 1996-12-01 |
| Access Restriction | Open |
| Subject Keyword | Immunology Antibodies Apoptosis Hiv Fas Immunoblotting Domain Recombinant Human V3 Loop Gp120 V3 Journal: The Journal of experimental medicine (Vol- 184, Issue- 6) |
| Content Type | Text |
