Pathogenic autoreactive T-cell clonotypes

Pathogenic autoreactive T-cell clonotypes are specific lineages of T lymphocytes that express unique T-cell receptors (TCRs) capable of recognizing and attacking self-antigens (Roep & Peakman, 2012, Diabetologia). In healthy individuals, these cells are typically controlled by central and peripheral tolerance, but their escape and expansion lead to the development of autoimmune diseases such as Type 1 diabetes and multiple sclerosis (Kaskow & Baecher-Allan, 2018, Frontiers in Immunology). These clonotypes act as the primary effectors of tissue destruction by infiltrating target organs and secreting pro-inflammatory cytokines (Davis et al., 2017, Nature). Therapeutic targeting of these cells aims to achieve immune resetting or selective depletion, as seen with drugs like Teplizumab, which targets the CD3 complex to modulate autoreactive T-cell function (Herold et al., 2019, NEJM). Emerging precision medicines utilize peptide-MHC complexes or TCR-sequencing to specifically identify and neutralize these pathogenic clones while sparing the broader immune repertoire (Peakman, 2021, Journal of Clinical Investigation).

Other names

Autoreactive T cellsSelf-reactive T-cell clonesPathogenic T-cell receptorsAutoantigen-specific T cellsDiabetogenic T cells

Selective depletion of autoreactive T cells, induction of immune anergy, modulation of T-cell receptor signaling, and inhibition of co-stimulatory pathways.