Abstract
T cells help orchestrate immune responses to pathogens, and their aberrant regulation can trigger autoimmunity. Recent studies highlight that a threshold number of T cells (a quorum) must be activated in a tissue to mount a functional immune response. These collective effects allow the T cell repertoire to respond to pathogens while suppressing autoimmunity due to circulating autoreactive T cells. Our computational studies show that increasing numbers of pathogenic peptides targeted by T cells during persistent or severe viral infections increase the probability of activating T cells that are weakly reactive to self-antigens (molecular mimicry). These T cells are easily re-activated by the self-antigens and contribute to exceeding the quorum threshold required to mount autoimmune responses. Rare peptides that activate many T cells are sampled more readily during severe/persistent infections than in acute infections, which amplifies these effects. Experiments in mice to test predictions from these mechanistic insights are suggested.
Original language | English |
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Article number | e2318599121 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 121 |
Issue number | 11 |
DOIs | |
State | Published - 12 Mar 2024 |
Externally published | Yes |
Bibliographical note
Publisher Copyright:Copyright © 2024 the Author(s). Published by PNAS.
Keywords
- immunology
- | T cells
- | autoimmunity