Accepted theory is the human immune system attacks, and then develops (adaptive), B and T cells (lymphocytes) in response to previous disease-causing foreign viruses and/or bacteria. Malfunctioning immune system cells, known as autoreactive B and T cell lymphocytes cooperate to produce autoantibodies and cytotoxic effector T cells that can destroy pancreatic beta cells, resulting in type 1 diabetes (T1D).
Critical knowledge gaps and questions remain unresolved regarding the onset of T1D, suggesting involvement of other, unknown immune system factors. Our lab recently discovered an entirely new type of autoreactive lymphocyte that has features of both B cells and T cells. We refer to these hybrid lymphocytes as dual expressers or crossover (X) cells. Normally, these B and T cells express their traits separately. Our recently published data (Ahmed et.al.) indicate a major role for X cells in causing T1D by expressing the traits of B and T cells together.
The goal of this project is to build upon one of our findings and to further investigate how X cells expansion result in the onset of T1D. X cells in a T1D, unlike in a normal individual, express one dominant antibody that we refer to as the X-mAb. This antibody has the unique feature of having the same antigen binding site in all T1D patients examined so far. A second unique feature of X-mAb is its ability to look like insulin and activate killer immune cells in T1D patients.
Very limited information is available regarding autoreactive T cells which are recognized and stimulated by x-mAb. A better understanding of the x-mAb interaction with autoreactive T cells will provide new information. This could enable new diagnostic strategies to predict a high likelihood of a future pancreatic beta cell attack. In turn, an intervention may then be developed to disrupt the onset of T1D, thereby preventing the disease.