The Molecular Interaction of CAR and JAML Recruits the Central Cell Signal Transducer PI3K

Skin Reaction Lymphocytes in the skin known as γδ T cells provide an important barrier against infection and injury. Unlike classical αβ T cells, less is known about the molecular requirements of γδ T cell activation. Two studies demonstrate that the junctional adhesion molecule–like protein (JAML) is a costimulatory molecule for mouse γδ T. Witherden et al. (p. 1205 ; see the Perspective by Shaw and Huang ) showed that JAML, binding to its ligand Coxsackie and adenovirus receptor (CAR), leads to proliferation, as well as cytokine and growth factor production by γδ T cells. In vivo, JAML-CAR interactions contributed to the wound healing response in mice. Verdino et al. (p. 1210 ; see the Perspective by Shaw and Huang ) present a crystal structure of CAR/JAML, which revealed an intracellular signaling motif similar to that known for the αβ T cell costimulatory receptor that signals through phosphoinositide 3-kinase.