Hoyne, G. F. (2011). Mechanisms that regulate peripheral immune responses to control organ specific autoimmunity. Clinical and Developmental Immunology, 2011, 1-9.
The immune system must balance the need to maintain a diverse repertoire of lymphocytes to be able to fight infection with the need to maintain tolerance to self proteins. The immune system places strict regulation over the ability of T cells to produce the major T cell growth factor interleukin 2 as this cytokine can influence a variety of immune outcomes. T cells require the delivery of two signals one through the antigen receptor and a second through the costimulatory receptor CD28. The immune system uses a variety of E3 ubiquitin ligases to target signaling proteins that function downstream of the TCR and CD28 receptors. Mutations in these E3 ligases can lead to a breakdown in immune tolerance and development of autoimmunity. This review will examine the role of a range of E3 ubiquitin ligases and signaling pathways that influence the development of T cell effector responses and the development of organ specific autoimmune diseases such as type 1 diabetes.
Peer-reviewed, Autoimmunity, Diabetes, immune tolerance, T cells, Ubiquitin ligases