Differentiation marker-negative CD4<sup>+</sup>T cells persist after yellow fever virus vaccination and contribute to durable memory
Abstract Factors that contribute to durable immunological memory remain incompletely understood. In our longitudinal analyses of CD4+T cell responses to the yellow fever virus (YFV) vaccine by peptide-MHC tetramers, we unexpectedly found naïve phenotype virus-specific CD4+T cells that persisted months to years after immunization. These Marker negative T cells (TMN) lacked CD95, CXCR3, CD11a, and CD49d surface protein expression, distinguishing them from previously discovered stem-cell memory T cells. Functionally, they resembled genuine naïve T cells uponin vitrostimulation. Single-cell TCR sequencing detected expanded clonotypes within the TMNsubset and identified a shared repertoire with memory and effector T cells. T cells expressing TMN-associated TCRs were rare before vaccination, suggesting their expansion following vaccination. Longitudinal tracking of YFV-specific responses over the subsequent years revealed superior stability of the TMNsubset and their association with the longevity of the overall population. The identification of these long-lived, antigen-experienced T cells may inform the design of durable T cell-based vaccines and engineered T cell therapies..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 16. März Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Pan, Yi-Gen [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2024.03.11.584523 |
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| PPN (Katalog-ID): |
XBI042916941 |
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| 245 | 1 | 0 | |a Differentiation marker-negative CD4<sup>+</sup>T cells persist after yellow fever virus vaccination and contribute to durable memory |
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| 520 | |a Abstract Factors that contribute to durable immunological memory remain incompletely understood. In our longitudinal analyses of CD4+T cell responses to the yellow fever virus (YFV) vaccine by peptide-MHC tetramers, we unexpectedly found naïve phenotype virus-specific CD4+T cells that persisted months to years after immunization. These Marker negative T cells (TMN) lacked CD95, CXCR3, CD11a, and CD49d surface protein expression, distinguishing them from previously discovered stem-cell memory T cells. Functionally, they resembled genuine naïve T cells uponin vitrostimulation. Single-cell TCR sequencing detected expanded clonotypes within the TMNsubset and identified a shared repertoire with memory and effector T cells. T cells expressing TMN-associated TCRs were rare before vaccination, suggesting their expansion following vaccination. Longitudinal tracking of YFV-specific responses over the subsequent years revealed superior stability of the TMNsubset and their association with the longevity of the overall population. The identification of these long-lived, antigen-experienced T cells may inform the design of durable T cell-based vaccines and engineered T cell therapies. | ||
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| 700 | 1 | |a Su, Laura |4 aut | |
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