The genetics of proteasomes and antigen processing.

The T cell arm of the immune system of higher vertebrates is specific for antigenic peptides bound to cell surface major histocompatibility complex (MHC) molecules. These peptides are derived from two distinct pathways of antigen processing. The class I, or endogenous pathway, utilizes proteasomes and the ubiquitin system for protein degradation, with subsequent transport of the resulting peptides into the lumen of the endoplasmic reticulum by a specific peptide transporter, called TAP. The expression of distinct proteasome subsets is regulated by the cytokine gamma interferon (IFN-gamma). The class II, or exogenous pathway, utilizes the endosomal and lysosomal pathways for protein degradation, and a number of immune-specific accessory molecules including the class-II associated Invariant chain (Ii) and MHC-encoded HLA-DM (H2-DM in mouse) molecules.