Antigen-presenting cell
In addition to the MHC family of proteins, antigen presentation relies on other specialized signaling molecules on the surfaces of both APCs and T cells.
Some cancer therapies involve the creation of artificial APCs to prime the adaptive immune system to target malignant cells.
This is achieved by interacting with a professional APC which presents an antigen recognized by their T cell receptor.
[5] They are very efficient at internalizing antigens, either by phagocytosis (e.g. macrophages), or by receptor-mediated endocytosis (B cells), processing the antigen into peptide fragments and then displaying those peptides (bound to a class II MHC molecule) on their membrane.
The expression of co-stimulatory molecules and MHC class II are defining features of professional APCs.
They can also perform cross-presentation, a process by which they present exogenous antigen on MHC class I molecules to cytotoxic T cells.
[2] Dendritic cells also play a role in peripheral tolerance, which contributes to prevention of auto-immune disease.
[9] After this activation, macrophages are able to express MHC class II and co-stimulatory molecules, including the B7 complex and can present phagocytosed peptide fragments to helper T cells.
They use an MHC class I molecule coupled to beta-2 microglobulin to display endogenous peptides on the cell membrane.
These peptides originate within the cell itself, in contrast to the exogenous antigen displayed by professional APCs using MHC class II molecules.
Cytotoxic T cells are able to interact with endogenous antigen presented using an MHC class I molecule.
However, it has been observed that antigen presentation to CD4+ cells via MHC class II is not restricted to the classically professional APCs.
The internalized antigen is digested into smaller peptides containing epitopes, which are then presented to T cells by the MHC.
Some artificial APCs are derived from human cells; others are acellular, containing MHC proteins, co-stimulatory molecules and the necessary peptides.
[16][17] The APC activator IMP321 is being tested in clinical trials to accelerate the immune reaction to eliminate metastatic breast cancer or melanoma.
