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 “en-dogenous ” pathway provides peptides to MHC class I molecules for presentation to CD8 T cells. These pep-tides 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 pep-tides 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 pep-tides are derived from extracellular antigens taken up by endocytosis and degraded in the endosomal/lysosomal pathway. Peptide loading of MHC class H molecules re-quires 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 require-ment is unknown. The class II region of the MHC con-tains a cluster of genes encoding proteins involved in an-tigen processing, including genes for two proteasome subunits (LMP2 and LMP7), the peptide transporter heterodimer (TAP! and TAP2), and the H-2M/HLA-DM molecule (Ma and Mb, or DMA and DMB). J. Leukoc