iNKT cell autoreactivity: what is 'self' and how is it recognized?

Abstract

Invariant natural killer T (iNKT) cells are thought to be autoreactive by 'design'. Here, Laurent Gapin describes how iNKT cell autoreactivity might be triggered and proposes that several self lipids are probably involved in the positive selection of iNKT cells and the autoreactivity of these cells in peripheral tissues. Following stimulation through their T cell receptor, invariant natural killer T (iNKT) cells function as innate effector cells by rapidly releasing large amounts of effector cytokines and chemokines and therefore have an important role in modulating the ensuing immune response. iNKT cells recognize, and are activated by, diverse glycolipid antigens, many of which are found in microorganisms. However, iNKT cells also show some reactivity to 'self'. Here, I outline our current understanding of iNKT cell autoreactivity and propose that several self lipids are probably involved in the positive selection and autoreactivity of iNKT cells.