Not everyone who works with the metal becomes ill. About 85 percent of people who develop chronic beryllium disease have an immune system protein known as HLA-DP2. Cells throughout the body use this molecule to tell the immune system what is going on inside of them. HLA-DP2 sits on the cell surface holding small protein fragments taken from the cell's interior. Immune system sentinels known as T cells bump against HLA-DP2 and its displayed protein fragment. If the protein fragment is derived from the body's own proteins, the T cell ignores it; if it is a foreign peptide, say from a bacterium, virus or other pathogen, the T cell sounds the alarm and triggers an immune response. HLA-DP2 differs from most other peptide-presenting proteins by a single amino acid.
Dr. Kappler and his colleagues performed a series of highly detailed genetic, x-ray diffraction, molecular binding and electrostatic studies to show how this single amino acid can combine with other amino acids from HLA-DP2 and some of its bound self-peptides to create a unique molecular pocket that captures a single beryllium ion along with a sodium ion. The peptides that bind to HLA-DP2 come from the body's own tissues and normally elicit no immune response. With the beryllium and sodium firmly lodged in the molecular pocket, however, those peptides have a very slightly altered shape and electrical charge, which roving T cells recognize as foreign and dangerous. They initiate an immune response that causes inflammation and scarring in the lungs. "This response resembles allergic hypersensitivity in that a metal ion causes an allergic reaction," said Dr. Kappler. "But it also resembles autoimmunity in that the immune system is mounting an attack against a self-peptide. It is a new form of immune response, and may lead to new therapeutic strategies to treat and prevent the disease."
Source: Eurekalert