Immune cells take in unknown enemies

MHC class I molecules normally present endogenously synthesized antigens and thus activate cytotoxic T lymphocytes (CTLs). In antigen- presenting cells (APCs), however, some seemingly extracellular antigens are cross-presented: they are loaded onto the class I pathway in addition to their usual presentation by MHC class II. For example, APCs in mice were recently shown to activate antipoliovirus CTLs, despite lacking a receptor for the virus, presumably by cross-presenting poliovirus antigens on class I. But now Stefan Freigang, Rolf Zinkernagel, and colleagues (University of Zurich, Zurich, Switzerland) show that the missing receptor does not stop viral uptake in APCs, suggesting that cross-presentation is not needed as an explanation.

“Even in a situation where everybody would suspect that cross-presentation is going on, we see that APCs are taking in the virus,” says Freigang. His group finds viral RNA in APCs of the receptorless mice. Further, the RNA had to be translated to elicit CTL responses. Thus, even if cross-presentation—which does not require translation—might occur, it is too inefficient under physiological infection conditions to cause an immune response.

Not all cells are susceptible to viral infection, since only transgenic mice expressing the poliovirus receptor develop disease symptoms. So what is special about APCs is not clear. “We can only speculate on how the virus gets into the cell,” says Freigang. Perhaps a subset of APCs has the ability to take in a variety of pathogens with a nonspecific receptor. ▪

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