The Role of Protein and Lipid Clustering in Lymphocyte Activation

Lymphocytes must strike a delicate balance between activating in response to signals from potentially pathogenic organisms and avoiding activation from stimuli emanating from the body’s own cells. For cells, such as T or B cells, maximizing the efficiency, fidelity and minimizing the cross-talk of complex signalling pathways is crucial. One way of achieving this control is by carefully orchestrating the spatio-temporal organization of signalling molecules, thereby regulating the rates of protein-protein interactions. This is particularly true at the plasma membrane where proximal signalling events take place and the phenomenon of protein microclustering has been extensively observed and characterized. This review will focus on what is known about the principles governing the heterogeneous distribution of proteins and lipids at the cell surface, illustrating how such distributions can influence signalling in health and disease. We particularly focus on nanoscale molecular organization, which has recently become accessible for study through advances in microscope technology and analysis methodology.