In multiple sclerosis (MS), the myelin that surrounds the axons of nerve cells is attacked by the body?s own T cells, resulting in slowed and disrupted nerve impulses and, ultimately, axon loss.
Myelin basic protein (MBP) is a major component of the myelin sheath and when used as an antigen will induce experimental autoimmune encephalitis (EAE) in mice, which is used as an animal model of human MS.
Interestingly, myelin-specific T cells are found in both healthy individuals as well as patients with MS, thus researchers have been working to determine what specific characteristic of these destructive T cells is dominant in driving the development of EAE/MS. In a study appearing online on July 12 in advance of publication in the August print issue of the Journal of Clinical Investigation, Eli Sercarz and colleagues from the Torrey Pines Institute for Molecular Studies immunized mice with an epitope of MBP known as Ac1?9, which resulted in a single episode of EAE in these animals, followed by recovery and resistance to any reinduction of disease. The authors then went on to characterize the Ac1?9?specific T cells present during the induction, onset, and recovery from disease. They identified two distinct subsets of T cells, or clonotypes, soon after immunization and prior to disease onset: BV8S2/BJ2S7 and BV16/BJ2S5.
The BV8S2/BJ2S7 clonotype was found in far greater excess, disappeared with disease recovery, and was found to transfer disease to other healthy mice. The second clonotype, BV16/BJ2S5, persisted following recovery, consistent with the hypothesis that the other, BV8S2/BJ2S7 T cell clonotype, is the driver of disease and necessary for EAE/MS persistence. The identification of this T cell subset suggests that these cells may be critical targets valuable to the design of therapies for autoimmune diseases such as MS.
TITLE: A public T cell clonotype within a heterogeneous autoreactive repertoire is dominant in driving EAE