I. An Introduction to T Cell Tolerance
II. Transcription Factor Aire Orchestrates T Cell Tolerance
Part I: An Introduction to T Cell Tolerance
|Download: High Res Low Res|
|Resources: Related ArticlesRecorded: 2016|
|Trouble Viewing? Try it on iTunes.Report a problem.|
To successfully fight off microbial infections, our immune systems must recognize a broad and diverse array of peptides. Occasionally, this results in the recognition of self-peptides and the development of autoimmune disease. For example, if a T cell recognizes insulin, type-1 diabetes may result. In her first talk, Dr. Mathis explains how the body has developed multiple mechanisms of immunological tolerance to prevent self-recognition. She focuses in greater detail on two particular types of T cell tolerance: clonal deletion and suppression.
Patients with Autoimmune Polyglandular Syndrome Type-1, a disease that manifests as autoimmune attacks on many organs, are known to have a mutation in the transcription factor Aire. Aire is expressed in a small subset of cells in the thymus, so how does it cause autoimmune disease in so many tissues? In Part 2, Dr. Mathis describes experiments from her lab showing that Aire regulates the transcription of many self-antigens in the thymus. Expression of these self-antigens is required for the development of T cell tolerance; if Aire is mutated, autoimmunity results.
Diane Mathis is a Professor in the Division of Immunology and the Department of Microbiology and Immunobiology at Harvard Medical School. She is also a principal member of the Harvard Stem Cell Institute and an associate member of the Broad Institute. Mathis’ lab studies the genetic, cellular and molecular mechanisms that determine immunological tolerance, and autoimmune diseases such as type-1 diabetes and autoimmune polyglandular syndrome that result when immunological self-tolerance fails. The lab focuses particularly on T cell tolerance. Learn more about Mathis’ research here.
Mathis’ scientific excellence has been recognized by election to the US National Academy of Sciences, the German National Academy of Sciences Leopoldina, and the American Academy of Arts and Sciences. Mathis is also an active member of the scientific community reviewing for numerous journals, organizing meetings, and teaching. She was chosen as the 2017 recipient of the FASEB Excellence in Science Award.
Diane Mathis received her BSc from Wake Forest University and her PhD from the University of Rochester. She was a post-doctoral fellow at the Laboratoire de Génétique Moléculaire des Eucaryotes in Strasbourg, France and at Stanford University.
- Ira Mellman iBioSeminar: Cell Biology of the Immune Response
- Ira Mellman iBioEducation: The Immune System
- Michael Dustin iBioSeminar: The Immunological Synapse
- Avery August iBioSeminar: Allergies and the Immune System
Xing Y, Hogquist KA. (2012) T-cell tolerance: central and peripheral. Cold Spring Harb Perspect Biol. 4(6).
Klein L, Kyewski B, Allen PM, & Hogquist KA. (2014) Positive and negative selection of the T cell repertoire: what thymocytes see (and don't see). Nat Rev Immunol. 14;377-391.
Anderson MS, Venanzi ES, Klein L, Chen Z, Berzins SP, Turley SJ, von Boehmer H, Bronson R, Dierich A, Benoist C, Mathis D. (2002) Projection of an immunological self shadow within the thymus by the aire protein.Science. 298:1395-401.
Abramson J, Giraud M, Benoist C, Mathis D. (2010) Aire's partners in the molecular control of immunological tolerance.Cell. 140:123-35.
Yang S, Fujikado N, Kolodin D, Benoist C, Mathis D. (2015) Immune tolerance. Regulatory T cells generated early in life play a distinct role in maintaining self-tolerance. Science. 348:589-94.
Bansal K, Yoshida H, Benoist C, Mathis D.(2017) The transcriptional regulator Aire binds to and activates super-enhancers. Nat Immunol. doi:10.1038/ni.3675