Immunorepertoire: New slant on personalized medicine

circulating tumor cell chip

The immune system is almost always described in martial terms. Immune (T and B) cells “patrol” the blood, looking for pathogenic “invaders”. Antibodies refine their ability to “combat” germs by repeated exposure, like a tactical squad learning the patterns of their enemies. Autoimmune diseases and allergies are caused by overzealous immune cells who attack harmless substances, like peanuts and dust mites, because they mistake them for the enemy.

T and B cells are always circulating in the blood and lymph, and they provide a record of all of the substances to which any given individual has been exposed over her lifetime. Jian Han, at the HudsonAlpha Institute for Biotechnology, wants to examine the aggregate of all these exposures – what he deems a person’s “immunorepertoire.” He thinks that monitoring this repertoire over time could provide a valuable assessment of someone’s overall health. Whenever something goes awry in the body, the immune system is probably working on it before any doctor or patient is aware of it.

“The immune system has already made a diagnosis,” he said. “If only we could read it!”

Han is comparing the immunorepertoires of healthy and sick people to see if diseases leave certain signatures, and has found that they do. People with ailments have a severely reduced immunorepertoire compared to healthy people – their complement of antibodies is much less diverse. To use the military analogy: when there is trouble in a particular sector from a particular disease, a response must be mustered and the size of the “standing army” – the immunorepertoire – shrinks as forces are deployed. Immunodiversty plummets before people feel sick, an early warning sign that the immune system is preparing for battle. Han is hoping an assessment of one’s immunorepertoire can one day be used for diagnostic purposes.

Immunity relies on T cells learning to distinguish self from non-self. Immune cells that react to our ourselves are what cause autoimmune diseases, like celiac disease and type I diabetes. Immune cells that recognize foreign invaders must then figure out which are harmful and which are not. All of the cells in our bodies – muscle cells, skin cells, nerve cells, bone cells – are identified by the proteins they present for examination by T cells. The T cells use receptor sites to “check” any protein they encounter and determine whether it is benign. But cells contain many, many harmless proteins – byproducts of normal cellular processes – how can T cell receptors possible comb through all of them to find the dangerous ones produced by viruses and bacteria?

The answer came in the 1980s when Mark Davis and his lab-mates revealed that T cell receptors, like antibodies, are made up of gene segments that can be mixed and matched to form many different combinations. Some of these gene segments are highly prone to mutation, which further varies the T cell sequences and allows them to recognize the myriad protein fragments constantly being presented to them by all the cells in the body. The sum total of the T cell receptors and antibodies circulating in someone’s body – his or her immunorepertoire – thus provides a snapshot of all of the foreign proteins that have ever been there.

While Han investigates the immune signatures of thirty different diseases, we are left with a dizzying prospect: the immune system never forgets. Now that we can analyze the massive amount of data contained in the immune system, what new patterns might emerge? Patient medical histories are notoriously prone to gaps, mistakes, and misinterpretations – might our immunorepertoire tell us more than a lifetime of doctor’s notes ever could?

Diana Gitig is a freelance science writer based in New York. Follow her @dmgitig

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