Single-cell fate mapping reveals widespread clonal ignorance of low-affinity T cells exposed to systemic infection

Justin Leube, Anton Mühlbauer, Immanuel Andrä, Madleen Biggel, Dirk H. Busch, Lorenz Kretschmer, Veit R. Buchholz

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

T cell ignorance is a specific form of immunological tolerance. It describes the maintenance of naivety in antigen-specific T cells in vivo despite the presence of their target antigen. It is thought to mainly play a role during the steady state, when self-antigens are presented in absence of costimulatory signals and at low density or to T cells of low affinity. In how far antigen-specific T cells can also remain clonally ignorant to foreign antigens, presented in the inflammatory context of systemic infection, remains unclear. Using single-cell in vivo fate mapping and high throughput flow cytometric enrichment, we find that high-affinity antigen-specific CD8+ T cells are efficiently recruited upon systemic infection. In contrast, most low-affinity antigen-specific T cells ignore the priming antigen and persist in the naïve state while remaining fully responsive to subsequent immunization with a high-affinity ligand. These data establish the widespread clonal ignorance of low-affinity T cells as a major factor shaping the composition of antigen-specific CD8+ T cell responses to systemic infection.

Original languageEnglish
Article number2250009
JournalEuropean Journal of Immunology
Volume53
Issue number3
DOIs
StatePublished - Mar 2023

Keywords

  • T cell ignorance
  • T cell receptor affinity
  • T cell recruitment
  • T cell tolerance
  • single-cell fate mapping

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