Trans-presentation: a novel mechanism regulating IL-15 delivery and responses

Immunol Lett. 2010 Jan 4;127(2):85-92. doi: 10.1016/j.imlet.2009.09.009. Epub 2009 Oct 7.

Abstract

Interleukin (IL)-15 is a cytokine that acts on a wide range of cell types but is most crucial for the development, homeostasis, and function of a specific group of immune cells that includes CD8 T cells, NK cells, NKT cells, and CD8 alpha alpha intraepithelial lymphocytes. IL-15 signals are transmitted through the IL-2/15R beta and common gamma (gamma C) chains; however, it is the delivery of IL-15 to these signaling components that is quite unique. As opposed to other cytokines that are secreted, IL-15 primarily exists bound to the high affinity IL-15R alpha. When IL-15/IL-15R alpha complexes are shuttled to the cell surface, they can stimulate opposing cells through the beta/gamma C receptor complex. This novel mechanism of IL-15 delivery has been called trans-presentation. This review discusses how the theory of trans-presentation came to be, evidence that it is the major mechanism of action, the current understanding of the cell types thought to mediate trans-presentation, and possible alternatives for IL-15 delivery.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Feedback, Physiological
  • Homeostasis
  • Humans
  • Immunity, Cellular
  • Immunologic Memory
  • Interleukin Receptor Common gamma Subunit / immunology*
  • Interleukin Receptor Common gamma Subunit / metabolism
  • Interleukin-15 / immunology*
  • Interleukin-15 / metabolism
  • Protein Transport / immunology
  • T-Lymphocytes / immunology

Substances

  • Interleukin Receptor Common gamma Subunit
  • Interleukin-15