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, ut ilizes proteasomes and the ubiquitin system for protein degradation, w ith subsequent transport of the resulting peptides into the lumen of t he endoplasmic reticulum by a specific peptide transporter, called TAP . The expression of distinct proteasome subsets is regulated by the cy tokine gamma interferon (IFN-gamma). The class II, or exogenous pathwa y, utilizes the endosomal and lysosomal pathways for protein degradati on, and a number of immune-specific accessory molecules including the class-II associated Invariant chain (I-i) and MHC-encoded HLA-DM (H2-D M in mouse) molecules.