Article

Mechanisms That Regulate Peripheral Immune Responses to Control Organ-Specific Autoimmunity

School of Health Sciences, University of Notre Dame Australia, 19 Mouat Street, Fremantle, WA 6959, Australia.
Clinical and Developmental Immunology (Impact Factor: 2.93). 04/2011; 2011:294968. DOI: 10.1155/2011/294968
Source: PubMed

ABSTRACT 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 paper 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.

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