the genome called HLA for "human leukocyte antigen"are known to dramatically increase risk of coming down with the condition.
These three genes encode molecules that present peptides (protein fragments) to the body's T cells. T cells then determine whether the peptide being presented is dangerous and needs to be eliminated from the bodyas in the case of foreign invaders such as bacteria or virusesor whether the peptide is "self," part of the host and something the immune system needs to leave alone. However, in the context of type 1 diabetes, T cells aggressively attack the body's own cells.
The scientists wanted to know on a molecular level how mutations in the immune surveillance machinery could lead to type 1 diabetes.
"We were interested in trying to understand why certain MHC molecules (which are molecules in mice analogous to HLA molecules in humans) are linked to autoimmune disease, particularly type 1 diabetes," said Research Associate Adam Corper of the Wilson lab, who was first author of the paper with Kenji Yoshida of the Teyton lab. "In particular, we wanted to know why a single residue at position 57 on the β chain of HLA molecules seems to be linked to the disease."
Breaking Tolerance
In the new research, the team used a series of structural and biophysical studies to answer that question.
Previously, Teyton and Wilson labs had determined the structure of a "diabetogenic" MHC molecule and found that mutations to position 57 caused only subtle changes. It did not, as some had speculated, cause the molecule to become unstable and non-functional.
Now, in the new study the researchers found that diabetes-causing mutations changed the charge at one end of the MHC peptide-binding groove. In individuals not predisposed to type 1diabetes, MHC molecules usually have a negatively charged residue at position 57. In contrast, disease-causing MHC molecules have a neutral residue at posit
'/>"/>
| Contact: Keith McKeown kmckeown@scripps.edu 858-784-8134 Scripps Research Institute Source:Eurekalert |
Related biology news :
1. New nano-tool synthesized at Scripps Research Institute
2. Scripps Research scientists solve mystery of fragile stem cells
3. Scripps research team reveals how an old drug could have a new use for treating river blindness
4. Scripps Research scientists find two compounds that lay the foundation for a new class of AIDS drug
5. Scripps Research scientists create new way to screen libraries of 10 million or more compounds
6. Scripps Research team wins global race to achieve landmark synthesis of perplexing natural product
7. Scripps Florida scientists show lifeless prions capable of evolutionary change and adaptation
8. Scripps research team develops technique to determine ethnic origin of stem cell lines
9. Scripps Research scientists crack mystery of proteins dual function
10. Scripps Research team uncovers chemical basis for extra quality control in protein production
11. Scripps research scientists find new link between insulin and core body temperature
| Copyright © 2003-2012 Bio-Medicine. All rights reserved. ABOUT | CONTACT US | DISCLAIMER | PRIVACY POLICY | TERMS AND CONDITIONS |  |