Immunity is a thankless job. Though the army of cells known as the immune system continuously keeps us safe from a barrage of viruses, bacteria and even precancerous cells, we mainly notice it when something goes wrong: "Why did I get the flu this year even though I got vaccinated?" "Why does innocent pollen turn me into a red-eyed, sniffling mess?"
A new study from Johns Hopkins takes a big step toward answering this and other questions about immunity, shedding light on how the body recognizes enemies on the molecular level -- and how that process can go wrong. The results appear Nov. 21, in the online journal Nature Communications.
In the laboratory of Scheherazade Sadegh-Nasseri, Ph.D., a professor of immunology and pathology at the Johns Hopkins University School of Medicine, research centers on how the immune system "selects" bits of protein to become so-called dominant epitopes. It's these red flags that white blood cells will be programmed to fight. Sadegh-Nasseri's research team spent years devising a mixture of proteins and chemicals that replicates the complex cellular processing that yields the dominant epitopes.
This is Scheherazade Sadegh-Nasseri of Johns Hopkins Medicine.
(Photo Credit: : Johns Hopkins Medicine)
"We wanted to know how one particular epitope becomes the dominant one that white blood cells look for when they're battling a given foe," Sadegh-Nasseri says.
Postdoctoral fellow AeRyon Kim, Ph.D., explains that the epitope-generating system enabled her and others on Sadegh-Nasseri's team to discriminate differences in the selection processes for proteins from pathogenic microbes versus human proteins: "We found that epitopes from human proteins that are associated with autoimmune diseases, like diabetes and rheumatoid arthritis, are generated through a different process than are proteins from pathogens." The pathogen-derived epitopes bind to protein receptors that protect them from the specialized processing enzymes that chop them up, the research group found. However, autoimmune-causing epitopes are resistant to destruction by those enzymes even without protection by their receptor proteins. Ultimately, Kim says, "When a critical mass of one epitope accumulates, it becomes dominant." The dominant epitope is then "presented" to newly minted T cells, which trains them to either destroy the foe or attack the body's own cells, ultimately causing inflammation.
"Knowing how these dominant epitopes arise -- and having a system that lets us predict which will be dominant -- is a big step toward understanding the roots of autoimmune diseases," says Sadegh-Nasseri. "It could also help in training the immune system -- for example, in vaccine development."
Source: Johns Hopkins Medicine