The Actin Cytoskeleton Controls the Activation of Invariant Natural Killer T Cells by Fine-Tuning CD1d Nanoscale Aggregation on Antigen Presenting Cells

Abstract

Invariant Natural killer T (iNKT) cells are a subset of lipid-specific T cells, restricted by the MHC-I class like molecule CD1d. A recent study showed a correlation between the co-localization of lipid-loaded CD1d molecules with lipid rafts on the membrane of antigen presenting cells, and their capacity of eliciting secretion of Th1-cytokines by stimulated iNKT cells [1]. Thus, this study suggested that not only the structure of CD1d bound to an exogenous lipid could influence Cd1d-mediated immunity, but also its partitioning on the membrane. Here, we address the spatiotemporal behaviour of α-Galactosylceramide loaded CD1d complexes on the cell membrane of human myeloid cells using multiple colour high-speed single-particle tracking (100 Hz) combined with an iNKT T Cell Receptor-Qdot conjugate as imaging probe. Furthermore, we complement these studies using STED nanoscopy to obtain nanoscale images of CD1d spatial organization. Our results indicate a direct role of the actin cytoskeleton in actively segregating CD1d nanoclusters on the cell membrane resulting in an inhibition of the activation of iNKT cells [2]. As a whole, our work proposes a new paradigm of biophysical interaction between CD1d presenting cells and NKT cells which deviates significantly from classical MHCI/II complexes and CD8/CD4-T Cells interactions.[1] J. S. Im et al., Immunity, 30, 888, 2009.[2] J. A. Torreno-Pina et al., in preparation.