Liposomes Targeted to Fc Receptors for Antigen Presentation by Dendritic Cells In Vitro and In Vivo∗

Abstract

The adaptive immune responses of mammals depend on cells specialized in the acquisition of antigen (Ag), called Ag presenting cells (APC), and cells that respond to that Ag, T and B lymphocytes. The two major arms of the adaptive immune response are antibody (Ab) production and cytotoxicity. T lymphocytes are divided into CD4+ and CD8+ T cells. CD4+ T cells are necessary to induce the immunoglobulin gene rearrangements necessary for the production of somatically mutated IgG Ab by B cells. Cytotoxicity is primarily a property of CD8+ T cells, but it requires CD4+ T-helper cells for complete differentiation and acquisition of effector functions. The induction of the immune response is thus a complex series of sequential interactions involving Ag contact with APC, APC contact with lymphocytes, and interaction among lymphocytes. Liposomes are very simple and lack microbial elements designed to inhibit immune responses and elements, such as endotoxin, repeated carbohydrates, and nucleic acids. CD4+ T cells do not recognize protein Ag as such but recognize Ag after uptake, partial proteolysis, and re-expression of Ag-derived peptides at the surface of APC in association with major histocompatibility complex (MHC)-encoded class II molecules. APC include dendritic cells (DC), macrophages, and B cells. DC is widely distributed in tissues, and both DC and macrophages use antibody secreted by B cells to bind Ag for enhanced presentation to naive CD4 T cells. DC and macrophages have receptors for Ag–Ab complexes, the immunoglobulin Fc receptors, which are a family of molecules at the surface of DC.