HIV vaccines induce CD8+ T cells with low antigen receptor sensitivity.
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| Title: | HIV vaccines induce CD8+ T cells with low antigen receptor sensitivity. |
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| Authors: | Migueles, Stephen A., Nettere, Danielle M., Gavil, Noah V., Wang, Lawrence T., Toulmin, Sushila A., Kelly, Elizabeth P., Ward, Addison J., Siying Lin, Thompson, Sarah A., Peterson, Bennett A., Abdeen, Cassidy S., Sclafani, Carina R., Pryal, Patrick F., Leach, Benjamin G., Ludwig, Amanda K., Rogan, Daniel C., Przygonska, Paulina A., Cattani, Angela, Imamichi, Hiromi, Sachs, Abraham |
| Source: | Science (pre-March 2025). 12/15/2023, Vol. 382 Issue 6676, p1270-1276. 7p. 5 Graphs. |
| Subjects: | Antigen receptors, T cells, AIDS vaccines, CD8 antigen, T cell receptors |
| Abstract: | Current HIV vaccines designed to stimulate CD8+ T cells have failed to induce immunologic control upon infection. The functions of vaccine-induced HIV-specific CD8+ T cells were investigated here in detail. Cytotoxic capacity was significantly lower than in HIV controllers and was not a consequence of low frequency or unaccumulated functional cytotoxic proteins. Low cytotoxic capacity was attributable to impaired degranulation in response to the low antigen levels present on HIV-infected targets. The vaccine-induced T cell receptor (TCR) repertoire was polyclonal and transduction of these TCRs conferred the same reduced functions. These results define a mechanism accounting for poor antiviral activity induced by these vaccines and suggest that an effective CD8+ T cell response may require a vaccination strategy that drives further TCR clonal selection. [ABSTRACT FROM AUTHOR] |
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| Database: | Psychology and Behavioral Sciences Collection |
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| Abstract: | Current HIV vaccines designed to stimulate CD8+ T cells have failed to induce immunologic control upon infection. The functions of vaccine-induced HIV-specific CD8+ T cells were investigated here in detail. Cytotoxic capacity was significantly lower than in HIV controllers and was not a consequence of low frequency or unaccumulated functional cytotoxic proteins. Low cytotoxic capacity was attributable to impaired degranulation in response to the low antigen levels present on HIV-infected targets. The vaccine-induced T cell receptor (TCR) repertoire was polyclonal and transduction of these TCRs conferred the same reduced functions. These results define a mechanism accounting for poor antiviral activity induced by these vaccines and suggest that an effective CD8+ T cell response may require a vaccination strategy that drives further TCR clonal selection. [ABSTRACT FROM AUTHOR] |
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| ISSN: | 00368075 |
| DOI: | 10.1126/science.adg0514 |
