Article Title

Mechanisms That Regulate Peripheral Immune Responses to Control Organ Specific Autoimmunity

UNDA Affiliation



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


Clinical and Developmental Immunology is an Open Access publication and this article may be accessed from the publisher here

Clinical and Developmental Immunology may be accessed from the National Library of Australia here

The Author:

Associate Professor Gerard Hoyne


Link to Publisher Version (DOI)