Concomitant increase in antigen binding and in T cell membrane lipid viscosity induced by the lymphocyte-activating factor, LAF.

Abstract

Abstract Lymphocyte-activating factor (LAF) is mitogenic for T cells and augments the mitogenicity of PHA in thymocyte cultures. Another factor of adherent cells (MF) increases the number of antigen-binding T cells in short-term cultures. In this study the two monokines were compared, and their role in T lymphocyte activation was investigated. It was found that both crude MF and partially purified LAF increase the lipid viscosity of the T cell membrane as measured by fluorescence depolarization of the lipid probe, l,6-diphenyl-1,3,5-hexatriene (DPH). The two monokines concomitantly increased lipid viscosity, were mitogenic, and increased antigen binding. These three biologic activities co-chromatographed both on Sephadex G-75 and on DEAE columns. The cell that responds to LAF with increased lipid viscosity and increased antigen binding was identified as a T cell of the Lyt-1+,2- class. The common separation characteristics and the identity of the target cell suggested that LAF and MF may be similar or even identical materials and that their biologic activities may be induced by one monokine. Causal connection between LAF-induced increased membrane viscosity and increased antigen binding was suggested by an experiment in which the rigidity of the lipid phase of T cells was increased by introducing cholesterol. We interpret these data to suggest that LAF is involved in the preparation of T cells for antigen binding, probably by increasing the accessibility of the receptor. The role of increased lipid viscosity in the unmasking of membrane bound antigens and receptors is discussed.