Peptide generation in the major histocompatibility complex class I antigen processing and presentation pathway

The bulk of antigens that are presented by major histocompatibility complex (MHC) class I molecules are processed in the cytosol. Therefore, the cellular protein degradation machinery is thought to play a major role in antigen processing. For example, there is clear evidence that the ubiquitin-proteasome pathway, the major proteolytic pathway in the cytosol, plays a role in the processing of class I-associated antigens. In addition, peptide chaperones must exist to properly target peptides to the transporter associated with antigen processing. Here, the author reviews some of the more important advances over the past year that further define the pathways of antigen breakdown in the cytosol. This includes a look at the distinctive roles of proteasomes versus immunoproteasomes, the isolation of peptide processing intermediates in the cytosol, and the role of defective ribosomal products. These findings highlight the importance of understanding basic cellular protein degradation pathways in antigen processing.