Posted on Oct 25, 2016, 10 a.m.
Researchers discover thousands of new immune system signals, calling their discovery the biological equivalent of discovering a new continent.
Imagine the immune system at work, sending out fighter cells to attack and destroy deadly pathogens like viruses and bacteria. Immune system cells seek out and latch onto the 'y-shaped' proteins of disease cells. These proteins called epitopes, stick out of the surface of the invader cells, and our immune system can then identify whether or not the cell is foreign or friendly. The purpose of immune system cells is to destroy these invaders, thereby preventing an uncontrolled infection. Published in the journal Science, researchers have discovered thousands of new epitope proteins that may uncover potential treatments to strengthen the immune system and provide new targets for immunotherapy and vaccine design. According to co-author of the study Professor Michael Stumpf, the new discovery is eqivalent to an astronomer finding a new planet in the solar system or a geographer discovering a new continent.
Spliced Epitopes Help Immune System Identify Cells
Researchers from Imperial College London have discovered that one-third of these epitope proteins are of a type called spliced epitopes and were once thought to be very rare. However, Scientists have developed new methods of mapping the surfaces of human cells which has lead to the discovery of thousands of these spliced proteins.
Before this study, scientists found that cells made their own signaling peptides (bonds of amino acid) on the cells surface. However, it is now known that cells can create spliced peptides by cutting proteins on the cell and rearranging these to create a new sequence. The new study has revealed that spliced epitopes comprise the majority of signaling epitopes that cells create and is how these cells can be identified by the immune system.
Overlapping Epitopes Cause of Autoimmune Diseases
With more epitopes for the immune system to scan, the higher the likelihood of detecting disease cells. However, there is a caveat, because healthy cells can overlap their own spliced epitopes, making the immune system misidentify them as harmful cells. This is the cause of autoimmune diseases, in which the immune system attacks healthy body tissue. Two autoimmune diseases that are caused by this effect are multiple sclerosis and Type 1 diabetes. However, now scientists are understanding how the immune system identifies cells through their epitopes and there is now hope for new therapies that may help the immune system to identify and attack only harmful cells.
The study of these new spliced epitopes could influence the design of new immunotherapies that will benefit patients with autoimmune disorders. Researchers have a difficult task in fully understanding the role that epitope proteins play in cell identification. These findings will help researchers to discover ways to boost the immune system to help manage autoimmune diseases, deliver new immunotherapy, and design new vaccines.
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Michele Mishto et al. A large fraction of HLA class I ligands are proteasome-generated spliced peptides. Science, October 2016 DOI: 10.1126/science.aaf4384