HIV vaccines induce CD8+ T cells with low antigen receptor sensitivity
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:382 |
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| Enthalten in: |
Science (New York, N.Y.) - 382(2023), 6676 vom: 15. Dez., Seite 1270-1276 |
| Sprache: |
Englisch |
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| Links: |
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| Anmerkungen: |
Date Completed 21.12.2023 Date Revised 29.12.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1126/science.adg0514 |
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| Förderinstitution / Projekttitel: |
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NLM36587065X |
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| 100 | 1 | |a Migueles, Stephen A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a HIV vaccines induce CD8+ T cells with low antigen receptor sensitivity |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
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| 700 | 1 | |a Ward, Addison J |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Siying |e verfasserin |4 aut | |
| 700 | 1 | |a Thompson, Sarah A |e verfasserin |4 aut | |
| 700 | 1 | |a Peterson, Bennett A |e verfasserin |4 aut | |
| 700 | 1 | |a Abdeen, Cassidy S |e verfasserin |4 aut | |
| 700 | 1 | |a Sclafani, Carina R |e verfasserin |4 aut | |
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| 700 | 1 | |a Przygonska, Paulina A |e verfasserin |4 aut | |
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