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Mice lacking key immune component still control chronic viral infections

weakened immune systems.

Immune system cells known as CD8 or cytotoxic T cells are responsible for recognizing virus-infected cells and killing them or sounding alarms that summon other defensive measures. To enable this recognition process, other cells regularly chop up viral proteins found in their interiors and display them on their surfaces. MHC Class I molecules act as a kind of stage for this inspection process, binding to the protein parts as they are sent to the surface and allowing CD8 T cells to recognize the presence of a foreign invader. When the CD8 T cells recognize a viral protein part, they either destroy the cell displaying the part or emit inflammatory hormones known as cytokines that trigger other immune defense measures.

Because the genetically modified mice used in their experiment lacked the genes that contain instructions for making MHC Class I molecules, Virgin and his colleagues expected to see little response from CD8 T cells when they injected the mice with herpes virus. Initially, that was exactly what they found.

"This was a study of chronic infection, though, and when we looked at the mice seven weeks later, we were surprised to find the mice making a very robust and effective CD8 T cell response," he says. "This suggests there's an alternate way of generating CD8 T cells."

The researchers believe a closely related stand-in for MHC Class I makes it possible for mouse CD8 T cells to recognize and fight the virus.

"It would be reasonable for there to be backup plans, particularly given that some viruses have evasion strategies that they use to block the classical antigen recognition processes that rely on MHC Class I," Virgin says.

Follow-up studies now underway have produced preliminary evidence that these backup plans may be active even when normal MHC Class I is engaged in the fight against chronic infection. Additional studies will look at whether the backup system can enable an ac
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Source:Washington University School of Medicine


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