Lipid raft-based membrane order is important for antigen-specific clonal expansion of CD4⁺ T lymphocytes

Lipid rafts are cholesterol and saturated lipid-rich, nanometer sized membrane domains that are hypothesized to play an important role in compartmentalization and spatiotemporal regulation of cellular signaling. Lipid rafts contribute to the plasma membrane order and to its spatial asymmetry, as well. The raft nanodomains on the surface of CD4⁺ T lymphocytes coalesce during their interaction with antigen presenting cells (APCs). Sensing of foreign antigen by the antigen receptor on CD4⁺ T cells occurs during these cell-cell interactions. In response to foreign antigen the CD4⁺ T cells proliferate, allowing the expansion of few antigen-specific primary CD4⁺ T cell clones. Proliferating CD4⁺ T cells specialize in their function by undergoing differentiation into appropriate effectors tailored to mount an effective adaptive immune response against the invading pathogen.

To investigate the role of lipid raft-based membrane order in the clonal expansion phase of primary CD4⁺ T cells, we have disrupted membrane order by incorporating an oxysterol, 7-ketocholesterol (7-KC), into the plasma membrane of primary CD4⁺ T cells expressing a T cell receptor specific to chicken ovalbumin_323–339 peptide sequence and tested their antigen-specific response. We report that 7-KC, at concentrations that disrupt lipid rafts, significantly diminish the c-Ovalbumin_323–339 peptide-specific clonal expansion of primary CD4⁺ T cells.

Our findings suggest that lipid raft-based membrane order is important for clonal expansion of CD4⁺ T cells in response to a model peptide.