Immunity Without Exposure

When a new bacterium or virus invades the body, the immune system mounts a "counter"-attack by sending in white blood cells called T-cells that are tailored to the molecular structure of that invader. Defeating the infection can take several weeks. However, once victorious, some T-cells stick around, turning into memory cells that remember the invader, reducing the time taken to kill it the next time it turns up.

Conventional thinking has it that memory cells for a particular microbe only form in response to an infection. "The dogma is that you need to be exposed," says Mark Davis of Stanford University in California, but now he and his colleagues have shown that this is not always the case. The team took 26 samples from the Stanford Blood Center. All 26 people had been screened for diseases and had never been infected with HIV, herpes simplex virus or cytomegalovirus. Despite this, Davis' team found that all the samples contained T-cells tailored to these viruses, and an average of 50 per cent of these cells were memory cells.

The idea that T-cells don't need to be exposed to the pathogen "is paradigm shifting," says Philip Ashton-Rickardt of Imperial College London, who was not involved in the study. "Not only do they have capacity to remember, they seem to have seen a virus when they haven't."

Electron microscope image of the H1N1 influenza virus,
which are 80-120 nanometres in diameter.

So how are these false memories created? To a T-cell, each virus is "just a collection of peptides", says Davis. And so different microbes could have structures that are similar enough to confuse the T-cells. To test this idea, the researchers vaccinated two people with an H1N1 strain of influenza and found that this also stimulated the T-cells to react to two bacteria with a similar peptide structure. Exposing the samples from the blood bank to peptide sequences from certain gut and soil bacteria and a species of ocean algae resulted in an immune response to HIV.  The finding could explain why vaccinating children against measles seems to improve mortality rates from other diseases. It also raises the possibility of creating a database of cross-reactive microbes to find new vaccination strategies. "We need to start exploring case by case," says Davis.

"You could find innocuous pathogens that are good at vaccinating against nasty ones," says Ashton-Rickardt. The idea of cross-reactivity is as old as immunology, he says. But he is excited about the potential for finding unexpected correlations. "Who could have predicted that HIV was related to an ocean algae?" he says. "No one's going to make that up!"