CD3 downregulation identifies high-avidity human CD8 T cells
© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology..
CD8 T cells recognize infected and cancerous cells via their T-cell receptor (TCR), which binds peptide-MHC complexes on the target cell. The affinity of the interaction between the TCR and peptide-MHC contributes to the antigen sensitivity, or functional avidity, of the CD8 T cell. In response to peptide-MHC stimulation, the TCR-CD3 complex and CD8 co-receptor are downmodulated. We quantified CD3 and CD8 downmodulation following stimulation of human CD8 T cells with CMV, EBV, and HIV peptides spanning eight MHC restrictions, observing a strong correlation between the levels of CD3 and CD8 downmodulation and functional avidity, regardless of peptide viral origin. In TCR-transduced T cells targeting a tumor-associated antigen, changes in TCR-peptide affinity were sufficient to modify CD3 and CD8 downmodulation. Correlation analysis and generalized linear modeling indicated that CD3 downmodulation was the stronger correlate of avidity. CD3 downmodulation, simply measured using flow cytometry, can be used to identify high-avidity CD8 T cells in a clinical context.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:215 |
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| Enthalten in: |
Clinical and experimental immunology - 215(2024), 3 vom: 19. Feb., Seite 279-290 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Clutton, Genevieve T [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 20.02.2024 Date Revised 09.04.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/cei/uxad124 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a © The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology. | ||
| 520 | |a CD8 T cells recognize infected and cancerous cells via their T-cell receptor (TCR), which binds peptide-MHC complexes on the target cell. The affinity of the interaction between the TCR and peptide-MHC contributes to the antigen sensitivity, or functional avidity, of the CD8 T cell. In response to peptide-MHC stimulation, the TCR-CD3 complex and CD8 co-receptor are downmodulated. We quantified CD3 and CD8 downmodulation following stimulation of human CD8 T cells with CMV, EBV, and HIV peptides spanning eight MHC restrictions, observing a strong correlation between the levels of CD3 and CD8 downmodulation and functional avidity, regardless of peptide viral origin. In TCR-transduced T cells targeting a tumor-associated antigen, changes in TCR-peptide affinity were sufficient to modify CD3 and CD8 downmodulation. Correlation analysis and generalized linear modeling indicated that CD3 downmodulation was the stronger correlate of avidity. CD3 downmodulation, simply measured using flow cytometry, can be used to identify high-avidity CD8 T cells in a clinical context | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CD8 + T cells | |
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| 650 | 4 | |a anti-viral immunity | |
| 650 | 4 | |a human | |
| 650 | 4 | |a tumor immunology | |
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| 700 | 1 | |a Weideman, Ann Marie K |e verfasserin |4 aut | |
| 700 | 1 | |a Mischell, Melissa A |e verfasserin |4 aut | |
| 700 | 1 | |a Kallon, Sallay |e verfasserin |4 aut | |
| 700 | 1 | |a Conrad, Shayla Z |e verfasserin |4 aut | |
| 700 | 1 | |a Shaw, Fiona R |e verfasserin |4 aut | |
| 700 | 1 | |a Warren, Joanna A |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Kuruc, JoAnn D |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Yinyan |e verfasserin |4 aut | |
| 700 | 1 | |a Gay, Cynthia M |e verfasserin |4 aut | |
| 700 | 1 | |a Armistead, Paul M |e verfasserin |4 aut | |
| 700 | 1 | |a G Hudgens, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Goonetilleke, Nilu P |e verfasserin |4 aut | |
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