Images Show How the Immune System Recognizes an Enemy

Clues to how the immune system identifies enemy threats may lead to new ways to prevent some diseases. Researchers from the Dana-Farber Cancer Institute, the Harvard Medical School and Argonne examined key immune system cells, using Structural Biology Center instruments at the Advanced Photon Source. The APS provides the nation’s most brilliant light for X-ray crystallography, a process that allows three-dimensional imaging of changes in crystals as they occur.

The three-dimensional images show that the cells’ docking equipment—the portion of the cells that allows linking with other cells—bind to a relatively short portion of the protein. The finding means that scientists can now focus on precisely that area when studying how the cells recognize harmful intruders and destroy those harmful cells. This understanding of the fundamental aspect of the human immune response to foreign proteins brings researchers a step closer to developing new ways of training the immune response to fight specific disorders, including infectious diseases and cancers.

The study involves immune cells called CD4 T cells, also known as “helper” T cells, whose job is to detect foreign invaders and organize an immune system attack against them. CD4 T cells are alerted to the presence of infection by amino acid compounds carried by invading bacteria and viruses. When a cell becomes infected, it displays these compounds of amino acids, called antigens, on its surface, as if to proclaim its distress to the immune system. The researchers created the first close-up, three-dimensional images of the coupling between the CD4 T cell receptor and antigens. The pictures suggest that no matter what peptide is involved, the T cell receptor will always bind to it with the same orientation.

The implications of the research extend far beyond their utility to researchers. Many human diseases, from infectious diseases like AIDS and hepatitis to genetic diseases like cancer, involve to some degree problems with CD4 T cells. When CD4 T cells are over-aggressive and attack healthy cells along with diseased cells, the result can be autoimmune diseases such as diabetes mellitus, multiple sclerosis and rheumatoid arthritis. When CD4 T cells fail to sound an alarm about diseased cells, the result is immune deficiency that can leave people vulnerable to infections and cancer. Knowing the precise mechanism by which CD4 T cells link up with antigens and how that mechanism can go awry can provide new insights into how to alter T cells to ward off these diseases.

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