It is well established that the immune system has sentinel cells whose job it is to report the presence of foreign invaders or cancers. In a process called crosspresentation, the sentinel cell internalizes foreign proteins, called antigens, from the environment and breaks them up into tiny fragments that are then displayed on the cell surface. Through this display the sentinel cell can then stimulate special immune cells called cytotoxic T lymphocytes to spring into action and battle the abnormal cells.
One of the ways that sentinel cells accomplish crosspresentation has been described in detail. Antigens are internalized into a specific compartment, transferred to the cytosol, chopped up by proteosomes, and then transported by the transporter associated with antigen processing (TAP) for display. However, there is some evidence that an alternative mechanism that does not involve TAP may also contribute to crosspresentation.
A research team led by Dr. Kenneth L. Rock from the Department of Pathology at the University of Massachusetts Medical School in Worcester examined the molecular mechanisms involved in the poorly understood TAP-independent crosspresentation pathway. By using chemical agents that differentially blocked one pathway and not the other, the TAP-independent pathway of presentation was shown to be distinct from the TAP-dependent pathway. This alternative pathway requires cysteine proteases and not proteosomes for chopping up proteins. The researchers went on to show that the cysteine protease Cat S plays a major role in generating presented proteins for the TAP-independent pathway of crosspresentation and contributes to immunity to viruses and transplanted tissues.
"We show unequivocally that this pathway is truly separate from the conventional TAP-dependent pathway. Having two distinct pathways involved in generating peptides, potentially in different amounts, could serve to increase the total number and diversity of peptides that are effectively presented and thereby broaden immune responses," says Dr. Rock. "This could also limit the ability of viruses to evade detection through their counter-surveillance mechanisms that block only one of these pathways."
Lianjun Shen, Luis J. Sigal, Marianne Boes, and Kenneth L. Rock: "Important Role of Cathepsin S in Generating Peptides for TAP-Independent MHC Class I Crosspresentation In Vivo"
Publishing in Immunity, Volume 21, Number 2, August 2004, pages 155-165.
Journal
Immunity