Influence of lipid rafts on pattern formation during T-cell adhesion

Abstract

Adhesion of T cells to antigen presenting cells is mediated by the TCR–MHCp and LFA1–ICAM1 protein complexes. These intercellular protein complexes segregate and form characteristic special patterns in the cell contact zone. Previous studies have attempted to explain the mechanisms of formation of these patterns. While emphasis has been put on membrane elasticity and active cytoskeletal transport, it remains unclear whether and how the pattern formation process is related to lipid rafts, which are nanoscale molecular clusters enriched in cholesterol and saturated phospholipids in cell membranes. Using Monte Carlo simulations of a statistical mechanical model for T-cell adhesion, we find that lipid rafts can lead to the formation of intermediate pattern with a ring of LFA1–ICAM1 complexes around a central domain of TCR–MHCp complexes even in the absence of active transport of T-cell receptor (TCR) molecules toward the center of the contact zone. In the presence of active TCR transport, lipid rafts can accelerate the formation of this monocentric pattern. We also find that lipid rafts have a strong stabilizing effect on the monocentric pattern after removal of the active TCR transport. Our results not only help to explain recent experimental observations, but also demonstrate that lipid rafts can cooperate with active cytoskeletal transport during the immunological synapse formation.

Keywords

• T-cell adhesion
• immunological synapse
• pattern formation
• lipid raft
• intercellular protein binding