The ins and outs of MHC class II-mediated antigen processing and presentation

To play their part in the generation of effective adaptive immune responses, different types of antigen-presenting cell (APC) take up and process antigen in different ways. The length of time that peptide–MHC class II complexes are present on APC surfaces can also vary depending on the cell type. This Review describes the different modes and mechanisms that regulate MHC class II processing and presentation. Antigenic peptide-loaded MHC class II molecules (peptide–MHC class II) are constitutively expressed on the surface of professional antigen-presenting cells (APCs), including dendritic cells, B cells, macrophages and thymic epithelial cells, and are presented to antigen-specific CD4+ T cells. The mechanisms of antigen uptake, the nature of the antigen processing compartments and the lifetime of cell surface peptide–MHC class II complexes can vary depending on the type of APC. It is likely that these differences are important for the function of each distinct APC subset in the generation of effective adaptive immune responses. In this Review, we describe our current knowledge of the mechanisms of uptake and processing of antigens, the intracellular formation of peptide–MHC class II complexes, the intracellular trafficking of peptide–MHC class II complexes to the APC plasma membrane and their ultimate degradation.