Re-shaping the T cell repertoire: TCR editing and TCR revision for good and for bad

Protection against the universe of pathogens requires a functional, diverse T cell repertoire. However, the price that is paid for an evolved, effective immune system includes the potential danger of generating autoaggressive T cells. Autoimmune diseases result from inherent breach of tolerance to self-antigens leading to disruption of the regulatory to autoaggressive T cell homeostatic balance. The immune system has evolved mechanisms to control those processes. For T cells, positive and negative selection in the thymus assures that only fully functional, non-self-reactive T cells will populate the periphery. Failure of this central tolerance would result in autoaggressive T cells escaping into the periphery. However, other means of escaping negative selection can occur in the periphery, i.e., TCR revision, or the altering of TCR expression after thymic egress. Here the potential benefits, i.e., expansion and re-shaping of the T cell repertoire as potentiated by TCR editing and revision are considered. Furthermore, the potential to develop autoaggressive TCR and thus enhance autoimmunity is considered.