Cholesterol-dependent plasma membrane order (Lo) is critical for antigen-specific clonal expansion of CD4+ T cells

Abstract

Abstract Early “T cell activation” events are initiated within the lipid microenvironment of the plasma membrane. Role of lipid membrane order (Lo) in spatiotemporal signaling through the antigen receptor in T cells is posited but remains unclear. We have examined the role of membrane order (Lo)/disorder (Ld) in antigen specific CD4+ T cell activation and clonal expansion by first creating membrane disorder, and then reconstituting membrane order by inserting cholesterol into the disordered plasma membrane. Significant revival of antigen specific CD4+ T cell proliferative response was observed after reconstituting the disrupted membrane order with cholesterol. These reconstitution experiments illustrate Koch’s postulate by demonstrating that cholesterol-dependent membrane order (Lo) is critical for responses generated by CD4+ T cells and point to the importance of membrane order and lipid microenvironment in signaling through T cell membrane antigen receptors.