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

• Published in: Clinical & developmental immunology 2011-01, Vol.2011 (2011), p.1-9
• Main Author: Hoyne, Gerard F.
• Format: Article
• Language: English
• Subjects: Animals; Autoimmune diseases; Autoimmunity - immunology; Clonal Anergy - immunology; Humans; Immune system; Immunology; Kinases; Lymphocyte Activation - immunology; Proteins; Repressor Proteins - metabolism; Review; Signal Transduction - immunology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; TOR Serine-Threonine Kinases - metabolism; Ubiquitin-Protein Ligases - immunology; Ubiquitin-Protein Ligases - metabolism
• ISSN: 1740-2522; 2314-8861; 1740-2530; 2314-7156
• DOI: 10.1155/2011/294968

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.