2020/11/30 by Robert Marsland, Marsland, Robert, Howell, Owen +4 · 2 citations
Immunology and Microbiology · #Adaptation and Self-Organizing Systems (nlin.AO) #Atherosclerosis and Cardiovascular Diseases #FOS: Biological sciences #FOS: Physical sciences #Immune Cell Function and Interaction #Populations and Evolution (q-bio.PE) #Soft Condensed Matter (cond-mat.soft) #Statistical Mechanics (cond-mat.stat-mech) #T-cell and B-cell Immunology #Tissues and Organs (q-bio.TO)
paper · pdf · doi:10.48550/arxiv.2012.00252
openalex publication_date 2020/11/30 · openalex created_date 2022/07/25 · openalex updated_date 2026/07/28
Regulatory T cells (Tregs) play a crucial role in mediating immune response.\nYet an algorithmic understanding of the role of Tregs in adaptive immunity\nremains lacking. Here, we present a biophysically realistic model of Treg\nmediated self-tolerance in which Tregs bind to self-antigens and locally\ninhibit the proliferation of nearby activated T cells. By exploiting a duality\nbetween ecological dynamics and constrained optimization, we show that Tregs\ntile the potential antigen space while simultaneously minimizing the overlap\nbetween Treg activation profiles. We find that for sufficiently high Treg\ndiversity, Treg mediated self-tolerance is robust to fluctuations in\nself-antigen concentrations but lowering the Treg diversity results in a sharp\ntransition -- related to the Gardner transition in perceptrons -- to a regime\nwhere changes in self-antigen concentrations can result in an auto-immune\nresponse. We propose a novel experimental test of this transition in\nimmune-deficient mice and discuss potential implications for autoimmune\ndiseases.\n