Molecular biology and immunology for clinicians 29: lipid domains, lipid rafts, and caveolae

The development of an antigen-specific immune response depends on the peptide-loaded MHC molecule on the surface of the antigen-presenting cell being found by the antigen-specific receptor on the cell about to be activated (the T-cell antigen receptor for T-cells or the membrane-bound immunoglobulin molecule on B-cells). The details of this process are becoming clear now with the appreciation of the supramolecular organization of the structures that make this cell-cell interaction. In the last 6 years has come an appreciation of the heterogeneity of the lipid bilayer membrane (a concept first put forth over 20 years ago), with certain lipids and membrane-bound proteins segregating into discrete ships called "lipid rafts" sailing in the surrounding more liquid lipid bilayer membrane. Knowledge of these microscopic structures leads to a better understanding of how antigen-specific responses are triggered and how aberrant responses are avoided; as one leader in the field put it, "keeping T-cells rested but ready."Membrane heterogeneity directly contributes to the rapid development of a more formalized cell-cell interaction that has been termed the "immunologic synapse." It is at this synapse that the acquired immune response, antigen specificity, is learned. In addition to antigen presentation, lipid rafts have also been implicated in signaling through a large number of receptors, endocytosis, cell interactions with pathogens and toxins, budding of viruses from host cell membrane, and the pathogenesis of prion disorders. Yet again, an insight in one discrete field of cell biology is proving to be of great relevance in a host of other areas of study.