Location is Everything: Lipid Rafts and Immune Cell Signaling

Abstract

The cells of both the adaptive and innate immune systems express a dizzying array of receptors that transduce and integrate an enormous amount of information about the environment that allows the cells to mount effective immune responses. Over the past several years, significant advances have been made in elucidating the molecular details of signal cascades initiated by the engagement of immune cell receptors by their ligands. Recent evidence indicates that immune receptors and components of their signaling cascades are spatially organized and that this spatial organization plays a central role in the initiation and regulation of signaling. A key organizing element for signaling receptors appears to be cholesterol- and sphingolipid-rich plasma membrane microdomains termed lipid rafts. Research into the molecular basis of the spatial segregation and organization of signaling receptors provided by rafts is adding fundamentally to our understanding of the initiation and prolongation of signals in the immune system.

Two Human ULBP/RAET1 Molecules with Transmembrane Regions Are Ligands for NKG2D

“…GPI-anchored proteins tend to be found in localized cholesterol-rich regions known as lipid rafts. Localized concentrations of specific surface proteins and signaling apparatus perform distinct roles in what has been referred to as the immune synapse (45). The ULBPs may be found preferentially in lipid rafts on cellular activation and synapse formation and would be found at high density in contact regions between cells.…”

Copatching and Lipid Raft Association of Different Viral Glycoproteins Expressed on the Surfaces of Pseudorabies Virus-Infected Cells

“…Interestingly, lipid rafts have been shown to collect or recruit specific signal transduction proteins at their cytoplasmic leaflet that are of critical importance in allowing capping of specific cellular surface proteins, such as the B-cell receptor (BCR) and T-cell receptor (TCR) (32,42,43). Indeed, antigen-stimulated lipid raft association of the BCR and TCR has been shown to allow these protein complexes to interact with raft-associated Src kinases, which subsequently phosphorylate specific tyrosinebased amino acid motifs (immunoreceptor tyrosine-based activation motifs) in the BCR and TCR as a first step in the signal transduction cascade leading to capping of the BCR and TCR and subsequent lymphocyte activation (6). The present data my therefore further support the hypothesis that has been put forward before (9) that the mechanism underlying capping of cross-linked viral glycoproteins, mediated by PRV gE and HSV gE, may be related to capping of cross-linked BCR and TCR in lymphocytes.…”

Cutting Edge: Oseltamivir Decreases T Cell GM1 Expression and Inhibits Clearance of Respiratory Syncytial Virus: Potential Role of Endogenous Sialidase in Antiviral Immunity

“…In cell-to-cell signaling, lipid rafts cluster and function as cell surface signaling platforms, as in the case of the immunological synapse (2). Cell surface proteins can be associated with or excluded from lipid rafts (3).…”