A central element of the immune system has remained constant through more than 400 million years of evolution, according to new research at National Jewish Health. In the September 29, 2011, online version of the journal Immunity, the researchers report that T-cell receptors from mice continue to function even when pieces of shark, frog and trout receptors are substituted in. The function of the chimeric receptors depends on a few crucial amino acids, found also in humans, that help the T-cell receptor bind to MHC molecules presenting antigens.
"These findings prove a hypothesis first proposed 40 years ago," said senior author Laurent Gapin, PhD, associate professor of immunology in the Integrated Deparemtn of Immunology at National Jewish Health and the University of Colorado Denver. "Even though mammals, amphibians and cartilaginous fish last shared a common ancestor more than 400 million years ago, they continue to share an element of their T-cell receptors, indicating that the T cell-MHC interaction arose early in the evolution of the immune system, and is central to its function."
The T cell serves as the sentinel, manager and enforcer of the adaptive immune response. It relies on its receptor, the T-cell receptor, to recognize foreign material and identify the target of the immune-system attack. When the receptor binds to small fragments of foreign organisms, called antigens, the T cell becomes activated, proliferates and initiates an attack against any molecule or organism containing that antigen.
T cells, however, cannot recognize free-floating antigens. They recognize antigens only when they are held by MHC molecules on the surfaces of other cells, much as a hotdog bun (MHC molecule) holds a hotdog (antigen). This interaction between the T cell and MHC molecules is crucial for immune defense and organ transplants. Compatibility of transplanted organs is determined by the similarity of different people's MHC molecules. Nonetheless,
|Contact: William Allstetter|
National Jewish Health