News & Research

    Dana-Farber Cancer Institute, Boston, Massachusetts

The role of HLA-DM in MHC class II linked susceptibility to type 1 diabetes

General Research Subject: Type 1 Diabetes

Focus: Genetics, Genetics\Type 1 Diabetes, Immunology, Other

Type of Grant: Mentor Based Postdoctoral Fellowship

Project Start Date: July 1, 2012

Project End Date: June 30, 2016

Research Description

Many genes can contribute to the development of type 1 diabetes, but individually most of these genes have only small effects.  The exception is the MHC region in the human genome because it accounts for a large fraction of the total genetic risk (40-50%).  In fact, typing for MHC genes is already used for prediction of type 1 diabetes, both in families and even in the general population.  Individuals who express the MHC proteins called DQ2 and DQ8 have a much higher risk for developing diabetes, and the risk is particularly high in individuals who express both DQ2 and DQ8.  These molecules present peptides to T cells and therefore play a central role in the disease by activating pathogenic T cell populations.  The goal of this project is to understand how peptides recognized by pathogenic T cells are bound by DQ2 and DQ8.  These studies will help us to understand how MHC genes contribute to the development of type 1 diabetes and may also help us to design novel approaches for treatment.

Research Profile

Mentor: Kai Wucherpfennig, MD, PhD  Postdoctoral Fellow: Wouter Pos, PhD

What area of diabetes research does your project cover?  What role will this particular project play in preventing, treating and/or curing diabetes?

This project deals with a central question in attempting to understand the mechanisms of genetic susceptibility to type 1 diabetes.  The most important susceptibility locus is the HLA region, in particular the HLA class II region on human chromosome 6.  HLA class II molecules present peptides from beta cell antigens to CD4 T cells, which are critical effector cells in islet inflammation.  The goal of this project is to determine how peptides are loaded onto HLA class II molecules by HLA-DM.  

If a person with diabetes were to ask you how your project will help them in the future, how would you respond?

The work is important because it defines the mechanisms by which beta cell peptides are presented to T cells.  A molecular understanding of this process may help us to use devise better approaches for the prevention of the disease.  

Why is it important for you, personally, to become involved in diabetes research?  What role will this award play in your research efforts?

My lab has actually worked in the diabetes field for more than 15 years.  The award will support the work of an outstanding postdoctoral fellow and stimulate his interest in the field.  

In what direction do you see the future of diabetes research going?

A central goal of the field is to develop safe approaches for prevention of the disease.