How persistent infection overcomes peripheral tolerance mechanisms to cause T cell–mediated autoimmune disease
Name
yin-et-al-2024-how-persistent-infection-overcomes-peripheral-tolerance-mechanisms-to-cause-t-cell-mediated-autoimmune.pdf
Description
Published version
Size
6.78 MB
Format
Adobe PDF
Checksum (MD5)
ffc9f51987bdf0599a3eccef37a1ee61
Author(s)
Yin, Rose
Melton, Samuel
Huseby, Eric S
Kardar, Mehran
Chakraborty, Arup K
Date Issued
March 6, 2024
Journal
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Citation
R. Yin,S. Melton,E.S. Huseby,M. Kardar, & A.K. Chakraborty, How persistent infection overcomes peripheral tolerance mechanisms to cause T cell–mediated autoimmune disease, Proc. Natl. Acad. Sci. U.S.A. 121 (11) e231859912 (2024).
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Physics
Ragon Institute of MGH, MIT and Harvard
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivatives
Persistent DSpace Link
DOI of Published Version
10.1073/pnas.2318599121
