There are two pathways through which to activate the T cells. In one pathway, called direct priming, the small pieces of viral protein presented on the pAPCs surfaces can be generated when the infected protein is made by pAPC. Alternately, the other pathway, known as cross-priming, involves transfer of some form of protein, previously thought to be peptides, to the pAPC where it can be presented to T cells.
"Although direct priming is relatively well-understood, less is known about cross-priming," Norbury said. "The prevailing hypothesis for cross-priming suggests that peptides are transported by carrier proteins from virus infected cells to pAPC."
Norbury and colleagues used vaccinia virus - the virus in the smallpox vaccine - and influenza A virus, in a mouse model to further investigate how the cross-priming pathway works. The team found that it is not peptides that are shared with recipient cells, but rather full-length, intact proteins. And, whereas, the previous theory suggested that proteasomes in the donor cell cut up the proteins into peptides prior to transfer to the recipient cell, Norbury's team found that the proteins are taken up by pAPCs and cut up after they are transferred to the recipient cells.
In a previous study, the team found that the protein pieces presented via direct priming are usually very short-lived but produce peptides very efficiently. However in cross-priming, because transfer to another cell takes time, rapidly degraded proteins are inefficient at generating peptides.
"Some viruses can only be seen via cross-presentation. Thus, it's important to make vaccines targeting both pathways," Norbury said. "If the proteins used in the vaccine are rapidly degrading, they will only target one pa
'"/>
Contact: Valerie Gliem
vgliem@psu.edu
814-865-9481
Penn State
27-May-2004