How persistent infection overcomes peripheral tolerance mechanisms to cause T cell-mediated autoimmune disease.
T cells
autoimmunity
immunology
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
12 Mar 2024
12 Mar 2024
Historique:
medline:
8
3
2024
pubmed:
6
3
2024
entrez:
6
3
2024
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 38446856
doi: 10.1073/pnas.2318599121
doi:
Substances chimiques
Autoantigens
0
Peptides
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2318599121Subventions
Organisme : National Science Foundation (NSF)
ID : DMR-2218849
Organisme : National Science Foundation (NSF)
ID : 2141064
Organisme : Ragon Institute of MGH, MIT and Harvard (Ragon Institute)
ID : 220568
Organisme : Massachusetts Institute of Technology (MIT)
ID : Physics of Living Systems Fellowship
Déclaration de conflit d'intérêts
Competing interests statement:A.K.C. is a consultant (titled Academic Partner) for Flagship Pioneering, serves as consultant and on the Strategic Oversight Board of its affiliated company, Apriori Bio, and is a consultant and SAB member of another affiliated company, Metaphore Bio. The other authors declare no competing interest.
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