Pathways for the processing and presentation of antigens to T cells

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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 II 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 hetcrodimer (TAPI and TAP2), and the H-2M/HLA-DM molecule (Ma and Mb, or DMA and DMB). J. Lcukoc. Biol. 57: 543–547; 1995.

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