Mechanisms of Antigen Presentation

Abstract T-lymphocytes recognize short peptide antigens bound stably to polymorphic major histocompatibility complex (MHC)-encoded glycoproteins expressed on the surface of antigen-presenting cells (APC). Two general pathways have evolved to generate peptide-MHC complexes. The MHC class II antigen processing pathway provides a mechanism for sampling proteins present in endosomal compartments. CD4+ regulatory T-cells recognize peptides bound to MHC class II molecules, which are selectively expressed in specialized APC that have efficient mechanisms for uptake of microbial antigens, and express costimulatory molecules required for activating naive T-cells. CD8+ T-cells recognize peptides bound to MHC class I molecules. Class I molecules are widely expressed and bind peptides derived from the normal turnover of cellular proteins, providing a mechanism to display a sampling of cellular components to be monitored for abnormalities by cytotoxic T-cells. Specialized accessory proteins influence the efficiency of antigen presentation and the specificity of immune responses through their roles in generating peptides, targeting antigen and MHC glycoproteins to selected intracellular compartments, and by direct participation in the peptide-loading mechanism. It has recently been discovered that some viruses have evolved ways to inhibit or subvert discrete steps in antigen processing, providing a mechanism to evade immune recognition.