Accepted_test

Somatic mutations may occur during cell division, and intensively dividing cells are more susceptible to acquiring such mutations. We hypothesized that somatic mutations can arise in T cells proliferating after activation during immune response, and some of such mutations may have functional consequences affecting cell survival, proliferation, and thus promoting persistence and dysregulation of T cell clones. Using peptide-MHC multimer cell sorting followed by whole exome sequencing of samples enriched for epitope-specific T cells, we discovered genomic variants associated with clonally expanded T cells involved in antiviral response or autoimmunity. The data obtained suggest that these variants represent somatic mutations that arise either during maturation or after activation and subsequent proliferation of naive precursors of the T cell clones. Although unique between donors and T cell types, some of the variants detected in different donors affect genes involved in processes of immune regulation and cell survival, implying their impact on the functional activity and persistence of the T cells.