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Human immunodeficiency virus-1 glycoproteins gp120 and gp160 specifically inhibit the CD3/T cell-antigen receptor phosphoinositide transduction pathway.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Céfai, D. Debré, Patrice Kaczorek, Michel Idziorek, Thierry Autran, Brigitte Bismuth, Georges |
| Copyright Year | 1990 |
| Abstract | The interference of the recombinant HIV-1 glycoproteins gp160 and gp120 with the CD3/T cell antigen receptor (TcR)-mediated activation process has been investigated in the CD4+ diphtheria toxoid-specific human P28D T cell clone. Both glycoproteins clearly inhibit the T cell proliferation induced in an antigen-presenting cell (APC)-free system by various cross-linked monoclonal antibodies specific for the CD3 molecule or the TcR alpha chain (up to 80% inhibition). Biochemical studies further demonstrate that exposure of the T cell clone to both glycoproteins (gps) specifically inhibits the CD3/TcR phospholipase C (PLC) transduction pathway, without affecting the CD3/TcR cell surface expression. Thus, inositol phosphate production, phosphatidic acid turnover, intracellular free calcium, and intracellular pH increase induced by CD3/TcR-specific MAbs are specifically impaired in gps-treated P28D T cells. Addition of purified soluble CD4 prevents binding of gps to T cells and overcomes all observed inhibitions. Maximal inhibitions are obtained for long-term exposure of the T cell clone to gps (16 h). No early effect of gps is observed. By contrast, gp160 and gp120 fail to suppress the CD2-triggered functional and biochemical P28D T cell responses. These results demonstrate that, in addition to their postulated role in the alteration of the interaction between CD4 on T lymphocytes and MHC class II molecules on APC, soluble HIV-1 envelope glycoproteins may directly and specifically impair the CD3/TcR-mediated activation of PLC in uninfected T cells via the CD4 molecule. |
| Starting Page | 1402 |
| Ending Page | 1405 |
| Page Count | 4 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://dm5migu4zj3pb.cloudfront.net/manuscripts/114000/114950/JCI90114950.pdf |
| PubMed reference number | 1979339v1 |
| Volume Number | 86 |
| Issue Number | 6 |
| Journal | The Journal of clinical investigation |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | CD4 Antigens Calcium ion Cellular Phone ENPEP gene Eighty HIV Envelope Protein gp120 HIV Envelope Protein gp160 Helper-Inducer T-Lymphocyte Immunologic Deficiency Syndromes Inositol Phosphates Leukemia, B-Cell Major Histocompatibility Complex Muromonab-CD3 Phosphatidic Acid Phosphatidylinositols Phospholipase C Psychological inhibition Receptors, Antigen Recombinants Toxoids diphtheria toxoid vaccine, inactivated polysaccharide-K transduction |
| Content Type | Text |
| Resource Type | Article |
