Antigen Processing

Abstract

Antigen presentation is an important mechanism by which the immune system recognises infection and maintains self‐tolerance. In order to effectively present antigens to T lymphocytes, intracellular enzymes degrade antigenic macromolecules into short fragments, which then bind major histocompatibility complex class I and class II molecules, or alternatively nonpolymorphic major histocompatibility complex class Ib molecules. This process of fragmentation is known as antigen processing and is shaped by the specificity of the enzymes involved as well as the intracellular compartments where processing takes place. Key players in antigen processing include cytoplasmic enzymes such as the proteasome and calpain, as well as cysteine cathepsins, aspartyl proteases, NADPH oxidase and GILT, which all reside in acidic vacuolar compartments. The trafficking of antigens to different intracellular compartments influences the sequence of processing and the selection of antigenic epitopes, which are displayed on the cell surface to promote immune activation or tolerance. Key Concepts Trafficking of antigens into proper compartments affects the degradation and availability of epitopes for both MHC‐I and MHC‐II presentation. Proteasome activity affects MHC‐I peptide generation and endogenous cytoplasmic peptide generation for MHC‐II. ROS production by NADPH oxidase can affect MHC‐I cross‐presentation and MHC‐II presentation. Cathepsin activity, which is regulated by endosomal pH, generates peptides for MHC‐I cross‐presentation and MHC‐II presentation. The reduction of disulphide bonds by GILT affects availability of epitopes for MHC‐II presentation. While homologous to MHC‐I, nonclassical MHC‐Ib acquire antigens processed in acidic compartments much like MHC‐II.