We would like to be able to know who will develop type 1 diabetes long before it happens and have a treatment ready that will stop it from happening. This is a tall order and the path to this goal is not a short one. However, an important step along this path was recently accomplished and the results published in this month’s issue of Immunity. The question addressed by this study is whether T cells which infiltrate the pancreas recognize pancreatic antigens or whether they don’t. Why does this matter? Well, it boils down to...

It has been estimated that approximately 50% of the genetic risk of developing type 1 diabetes is contributed by a single set of genes called the major histocompatibility complex (MHC). So what are they? Why is it such a major factor in determining the risk of developing this disease? What can we learn about type 1 by considering the MHC? It turns out that the MHC plays a very important role in the ability of our species to survive a pandemic. Their function is very well understood. They present antigen to T cells. First of all, we...

Today I want to talk about something full of strangeness and beauty which also is fundamental to the onset of type 1 diabetes – namely a process by which baby T cells mature into adult T cells. The process is called thymic selection. In the last couple of posts I talked about how T cells have receptors that recognize antigen. They arise from a fundamentally random process called recombination and are as likely to recognize insulin as to recognize a viral coat protein. How is it that the insulin reactive T cell is removed while the...

Each T cell and each B cell has a different antigen receptor.  Collectively T cells and B cells are referred to as lymphocytes. How many lymphocytes do we have? The answer is between 100 million and 1 billion. Now, let’s do a bit of math. Antigen receptors are constructed from two proteins (we call them subunits when they combine to make a single structure). Each of the proteins is coded in DNA as a gene. The problem here is that we may have 1 billion different antigen receptors but we sure don’t have 1 billion genes. In point...

I have this compulsion to talk about the immune system. In part this is because it is grant season and I have been writing a lot about it in my latest grant proposal. It is such a beautiful and strange thing that I want to display some of that strangeness and beauty to you. Also, it is fundamental to understanding Type 1 diabetes and the efforts we are making towards finding a cure. Come to think of it, one part of the immune system – namely the part that produces inflammation is pretty important for type 2 diabetes as well as type...

There are several forms of diabetes. The main forms are called Type 1 and Type 2. Here I will try to explain the underlying biology that leads to Type 1 diabetes. In the next post, I’ll tackle Type 2. Type 1 diabetes is very aggressive. Unlike Type 2, which can take a decade to develop, Type 1 can manifest in months. It is an autoimmune condition in which the insulin secreting cells of the pancreas (organized into structures called islets) are attacked by cells of the patient’s immune system. The reasons for this attack are...