101. The role of the PD-1 pathway in autoimmunity and peripheral tolerance.
- Author
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Fife, Brian T. and Pauken, Kristen E.
- Subjects
- *
T cells , *CELLULAR control mechanisms , *AUTOIMMUNITY , *CELL physiology , *CELL receptors , *BINDING sites - Abstract
Programmed death-1 (PD-1) is a surface receptor critical for the regulation of T cell function during immunity and tolerance. PD-1 interactions with its ligands PD-L1 and PD-L2 inhibit T cell effector functions in an antigen-specific manner. This paper examines the role of PD-1 in limiting autoreactivity and establishing self-tolerance and discusses the hypothesis that PD-1 ligand (PD-L) expression both spatially and temporally dictates the fate of self-reactive T cells during the breakdown of peripheral tolerance and development of autoimmunity. We focus our discussion on the role of PD-1/PD-L interactions during peripheral tolerance, the differential role for PD-L1 and PD-L2 in response to environmental or self-antigens, and the impact of PD-1 signaling on dynamic T cell motility and the T cell receptor (TCR) stop signal. Finally, we discuss the potential to selectively target the PD-1 pathway therapeutically to alter T cell function during autoimmunity. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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