Artificial antigen presenting cells
 | This article provides insufficient context for those unfamiliar with the subject. (November 2014) |
Artificial antigen presenting cells (aAPCs) are engineered platforms for T-cell activation. aAPCs are used as a new technology and approach to
Essential components of an aAPC
Signal 1
Signal 2
T cells need another signal to become activated in addition to Signal 1, this is done by co-stimulatory molecules such as the proteins CD80 (B7.1) or CD86 (B7.2), although other additional co-stimulation molecules have been identified. When Signal 2 is not expressed, but T cells receive Signal 1, the antigen-specific T cells become anergic and do not perform effector function.
Signal 3
Signal 3 is the aAPC secretion of stimulatory
Types of aAPCs
Cell-based aAPCs have been produced by transfecting murine
Many microparticle systems have been developed as microparticles represent physiologically similar sizes to cells. Microparticle curvature and shape has also been shown to play an important role in effective T cell stimulation.[3]
Materials which have been used include
Lipid based aAPC
In natural systems, the dynamic lipid bilayer is crucial for molecular interactions. Lipid bilayer-based particles with a fluid membrane have been developed as aAPCs to replicate interactions between natural APCs and T cells in nature. For instance, it has been observed that in vitro CD4+ T cell activation by MHC-containing liposomes results in T cell proliferation and IL-2 release. It showed how the lipid membrane functions as a support structure for antigen presentation.[7] Even in the absence of T cells, natural APCs have been found to precluster antigens. Researchers have created reconstituted liposomes with membrane microdomains enriched with epitope/MHC complexes to promote T cell proliferation.[8] A higher level of T cell activation is induced by the preclustering of MHC molecules.
Researchers also used solid particles as a core for the lipid bilayer to increase the stability of the liposomes. These are known as supported lipid bilayers (SLBs).[9] For example, nanoporous silica cores.
Polymeric aAPC
A variety of polymers have been added into aAPC systems, including biodegradable PLGA (Poly(lactic-co-glycolic acid)) and non-biodegradable sepharose or polystyrene beads. While IL-2 or other soluble molecules can be progressively released from within the aAPC, immunomodulatory substances (recognition and co-stimulatory ligands) can be attached to the surface of polymeric particles.[10]
The size and shape of microbeads are important parameters for T cell activation. The optimal size is 4 to 5 μm and optimal shape is non-spherical or ellipsoid, like natural APCs, to increase the contact area of the particles with the T cells.
Inorganic aAPC
Superparamgnetic particles can be used as aAPC for ex-vivo T cell expansion. These particles can be covalently bound to stimulatory ligands.[11] Another type of aAPCs are high-surface-are carbon nanotubes coated with ligands. these nanotubes whoxed higher T cell activation and IL-2 secretion than other high-surface-area particles.[12]
Uses
aAPCs remove the need to harvest patient specific APCs such as