Pathways for the processing and presentation of antigens to T cells

Abstract

Two pathways exist within vertebrate cells to generate peptides for recognition by T cells. The "endogenous" pathway provides peptides to MHC class I molecules for presentation to CD8+ T cells. These peptides are derived from proteins synthesized or residing in the cytoplasm or nucleus, and involves proteasomes and the ubiquitin pathway of protein degradation, as well as a specific peptide transporter (TAP) that allows these peptides access to the lumen of the endoplasmic reticulum. The exogenous pathway provides peptides to MHC class II molecules for presentation to CD4+ T cells. These peptides are derived from extracellular antigens taken up by endocytosis and degraded in the endosomal/lysosomal pathway. Peptide loading of MHC class II molecules requires the presence of a molecule (H-2M in mouse, HLA-DM in humans) that is structurally related to MHC class II molecules, but the mechanistic basis of this requirement is unknown. The class II region of the MHC contains a cluster of genes encoding proteins involved in antigen processing, including genes for two proteasome subunits (LMP2 and LMP7), the peptide transporter heterodimer (TAP1 and TAP2), and the H-2M/HLA-DM molecule (Ma and Mb, or DMA and DMB).