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Scientists discover the mechanisms and function of a type of mysterious immune cell
Date:9/2/2010

cells need recognition of an antigen by the T cell receptor," Wilson explained. "And from studies on αβ T cells, we know that for most T cells, one signal is not sufficient; they need a second, or costimulatory signal. For αβ T cells, that process has been well described. What we didn't know going into this current study whether γδ T cells required a second signal or not."

These two papers do in fact identify a junctional adhesion molecule, JAML, as a new costimulatory receptor for γδ T cells that binds to the ligand CAR (coxsackie and adenovirus receptor) expressed on keratinocytes.

"When there's damage or disease, the molecules we've identified are up-regulated," said Wilson, "and signals that are transmitted through their interaction with each other costimulate a T cell response that aids in tissue repair or killing of tumors."

Deborah Witherden, a senior staff scientist in Havran lab, was first author of the study titled "The adhesion molecule JAML is a costimulatory receptor for epithelial γδ T cell activation" (also with Petra Verdino, Stephanie Rieder, Olivia Garijo, Robyn Mills, Luc Teyton, Wilson, and Havran, all of Scripps Research, and Wolfgang Fischer of the Salk Institute). Verdino, a research associate in the Wilson lab, was first author of the companion publication, "The molecular interaction of CAR and JAML recruits the central cell signal transducer PI3K" (with Witherden, Havran, and Wilson).

A Combined Effort

The Witherden et al. study showed that γδ T cells in the skin and intestine require costimulatory signals delivered to the T cells by JAML binding to CAR on damaged keratinocytes. This leads to full activation of the γδ T cells and allows them to help heal wounds.

To understand the details of how γδ T cells are costimulated, scientists needed to get a three-dimensional view of the molecular interactions
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Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert

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