Antigen Presentation Is the Process by Which Protein Fragments Are Complexed with MHC Products and Posted to the Cell Surface

The process by which foreign materials enter the immune system is the key step that determines the eventual outcome of an immune response. A successful adaptive immune response, which includes the production of antibodies and the generation of helper and cytotoxic T cells, cannot unfold without the involvement of professional APCs. It is these cells that acquire antigen, process it, and then display it in a form that can be recognized by T cells. The pathway by which antigen is converted into a form suitable for T-cell recognition is referred to as antigen processing and presentation.

The class I MHC pathway focuses predominantly on presentation of proteins synthesized by the cell itself (including pathogen-encoded proteins in infected cells), whereas the class II MHC pathway is centered on materials acquired from outside the APC. Recall that all nucleated cells express class I MHC products, or can be induced to do so; this makes sense in view of the fact that a nucleated cell is capable of synthesizing nucleic acids as well as proteins and can thus in principle sustain replication of a viral pathogen. The ability to alert the immune system to the presence of an intracellular invader is inextricably linked to class I MHC-restricted antigen presentation. The distinction between the presentation of materials synthesized by an APC itself and the processing and presentation of antigen acquired from outside the cell is by no means absolute. Together, the class I and class II pathways of antigen processing and presentation sample all of the compartments that need to be surveyed for the presence of pathogens.

Antigen processing and presentation in both the class I and class II pathways may be divided into six discrete steps that are useful in comparing the two pathways: (1) acquisition of antigen, (2) tagging the antigen for destruction, (3) proteolysis, (4) delivery of peptides to MHC molecules, (5) binding of peptide to a MHC molecule, and (6) display of the peptide-loaded MHC molecule on the cell surface. Here we describe the molecular details of each pathway.