biostudies-literatureYin RRagon Institute of MGH, MIT and Harvard (Ragon Institute)Massachusetts Institute of TechnologyMassachusetts Institute of Technology (MIT)Ragon Institute of MGH, MIT and HarvardNational Science Foundation (NSF)National Science Foundatione2318599121https://www.ebi.ac.uk/biostudies/studies/S-EPMC10945823biostudies-literatureUnknown121(11)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 responsesProceedings of the National Academy of Sciences of the United States of AmericaHow persistent infection overcomes peripheral tolerance mechanisms to cause T cell-mediated autoimmune disease.PMC10945823Physics of Living Systems Fellowship2141064220568DMR-2218849Melton SHuseby ESChakraborty AKYin RKardar MfalseHow persistent infection overcomes peripheral tolerance mechanisms to cause T cell-mediated autoimmune disease.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 responses2024-01-01T00:00:00Z2024 Mar2025-04-22T05:34:39.839Z2024-11-15T04:37:01.848ZS-EPMC109458233844685610.1073/pnas.2318599121