Grad student's innovative research leads to immunology discovery
By Trevor Pritchard
By thinking "outside the box," Department of Microbiology and Immunology graduate student Nathan Peters has redefined the way we understand the human immune system.
"A classical question in immunology," begins Peters, "is how the immune system has the ability to recognize virtually any foreign invader without generating an immune response against [one's] own body."
Immune responses are controlled by a particular type of white blood cell known as a CD4 T-helper cell, which Peters calls "the quarterback of the immune system." Produced in a person's bone marrow and developed in the thymus, CD4 T-cells guide the immune system's attack on any foreign substance introduced, willingly or unwillingly, into the body. They are designed to recognize certain proteins - commonly called antigens - derived from these foreign agents.
One remarkable characteristic of the CD4 T-cells, says Peters, is their specificity. Each CD4 T-cell has a receptor molecule that will only recognize individual peptides, small sections of each protein, meaning that the human body must produce a staggering number of these cells to be able to successfully fend off disease.
"The generation of the T-cell receptor is a random process," says Peters. "It's very important in order that T-cells can recognize basically anything considered foreign."
This process, while effective, comes with a high price. Because of the random generation of the receptor molecule, a certain percentage of CD4 T-cells will be designed to recognize and destroy the body's own proteins, rather than foreign organisms. In most cases, these "self-reactive" T-cells are deactivated when they encounter self-antigens in the thymus. Yet quite often the corresponding self-antigen is found elsewhere in the body, sometimes in vital organs.
And it's these cells that are of particular concern to Peters, because they can generate an immune response against the person's own body, leading to auto-immune disorders like diabetes or lupus.
"But normally," he continues, "in most people [auto-immune disorders] are prevented."
Realizing that there must be some mechanism inhibiting self-immunization, Peters speculated that CD4 T-cells might need to work co-operatively, not individually, to induce an immune response.
With the guidance of his supervisor, Dr. Peter Bretscher, Peters tested this co-operation hypothesis by looking at the nature of immune responses in mice. "We took a normal mouse which contained a population of cells specific for an antigen," says Peters, "and we inactivated a significant portion of [the mouse's] protein-specific T-cells."
Peters then immunized the mouse with the entire antigen and, as he had suspected, the CD4 T-cells that would normally target the other peptides on the protein were also inhibited. The initial deactivation of the first set of cells had prevented the necessary co-operation, and thus the generation of an immune response, from taking place.
The implications of Peters' experiments are thought to be quite significant for future immunological research. "[These findings] apply to every aspect of immunology," says Peters confidently. "Currently we think that CD4 T-cells are activated independently of other T-cells, and thus how the immune system works has been considered in these terms."
Peters' next stop is Bethesda, Maryland, where he will continue his work at the National Institute of Health, one of North America's foremost biomedical research facilities. He hopes to play an important role in the future application of his research.
"Now, when you design a vaccine, you have to take into account this co-operation and how this affects the type of immune response generated," he says. "How the immune system works, how we design vaccines, how we regard auto-immunity - all these things now need re-thinking."