Autoimmune diseases are widespread and notoriously difficult to treat. In part, this is because why the immune system attacks its own tissues in patients with these conditions remains poorly understood.
In a study recently published in Cell, researchers from Osaka University have revealed that the body’s own proteins with unusual structure trigger immune cells to unleash a wave of inflammation that leads to autoimmunity.
Autoimmune diseases develop when the body’s immune system mistakenly attacks its own tissues instead of fighting off foreign invaders like bacteria or viruses. However, it has long been a mystery why this happens, as the immune system has many checks and balances to make sure that it only reacts to ‘non-self’ triggers.
“T cells have been thought to discriminate between small fragments of protein derived from self and non-self proteins presented on the major histocompatibility complex II (MHC-II), and ‘trained’ not to respond self-antigens” explains senior author of the study Hisashi Arase.
However, when the MHC-II is missing a crucial piece called the invariant chain (Ii), it can present larger, misfolded self antigens, called neoself-antigens, to T cells.”
Hisashi Arase, Osaka University
Given that autoantibodies to neoself-antigens are frequently found in patients with autoimmune diseases, the researchers explored T cell reactivity in patients with lupus and in mice, in which Ii was depleted from adult. They also investigated the effect of Epstein–Barr virus (EBV) infection, a risk factor for lupus, on T cell reactivity to neoself-antigens.
“The results were striking,” says Shunsuke Mori, lead author. “We found that approximately 10% of clonally expanded T cell repertoire in lupus patients recognized neoself-antigens. Furthermore, induction of neoself-antigens induced lupus-like disease in mice, meaning that they mounted an immune response to the body’s own tissues, thereby causing autoimmune disease.”
Furthermore, the researchers found that reactivation of EBV, which most people are infected with but is usually dormant, increases the presentation of neoself-antigens on MHC-II through downregulating the expression of Ii, triggering the activation of T cells directed against the body. This could explain why EBV reactivation is linked to the onset or exacerbation of lupus.
“Our findings demonstrate that T cells discriminate self- and neoself-antigens and do not recognize neoself-antigens as self antigens, thus leading to the development of autoimmunity when neoself-antigens are presented on MHC-II,” says Arase.
This study substantially increases our understanding of self-tolerance of T cells as well as the causes of autoimmune disease by identifying neoself-antigens as a distinct class of antigens that trigger an inappropriate immune response. This insight into why the body begins to attack itself could help develop new treatments for autoimmune disorders like lupus.
Mori, S., et al. (2024) Neoself-antigens are the primary target for autoreactive T cells in human lupus. Cell. doi.org/10.1016/j.cell.2024.08.025.

News
By working together, cells can extend their senses beyond their direct environment
The story of the princess and the pea evokes an image of a highly sensitive young royal woman so refined, she can sense a pea under a stack of mattresses. When it comes to [...]
Overworked Brain Cells May Hold the Key to Parkinson’s
Scientists at Gladstone Institutes uncovered a surprising reason why dopamine-producing neurons, crucial for smooth body movements, die in Parkinson’s disease. In mice, when these neurons were kept overactive for weeks, they began to falter, [...]
Old tires find new life: Rubber particles strengthen superhydrophobic coatings against corrosion
Development of highly robust superhydrophobic anti-corrosion coating using recycled tire rubber particles. Superhydrophobic materials offer a strategy for developing marine anti-corrosion materials due to their low solid-liquid contact area and low surface energy. However, [...]
This implant could soon allow you to read minds
Mind reading: Long a science fiction fantasy, today an increasingly concrete scientific goal. Researchers at Stanford University have succeeded in decoding internal language in real time thanks to a brain implant and artificial intelligence. [...]
A New Weapon Against Cancer: Cold Plasma Destroys Hidden Tumor Cells
Cold plasma penetrates deep into tumors and attacks cancer cells. Short-lived molecules were identified as key drivers. Scientists at the Leibniz Institute for Plasma Science and Technology (INP), working with colleagues from Greifswald University Hospital and [...]
This Common Sleep Aid May Also Protect Your Brain From Alzheimer’s
Lemborexant and similar sleep medications show potential for treating tau-related disorders, including Alzheimer’s disease. New research from Washington University School of Medicine in St. Louis shows that a commonly used sleep medication can restore normal sleep patterns and [...]
Sugar-Coated Nanoparticles Boost Cancer Drug Efficacy
A team of researchers at the University of Mississippi has discovered that coating cancer treatment carrying nanoparticles in a sugar-like material increases their treatment efficacy. They reported their findings in Advanced Healthcare Materials. Over a tenth of breast [...]
Nanoparticle-Based Vaccine Shows Promise in Fighting Cancer
In a study published in OncoImmunology, researchers from the German Cancer Research Center and Heidelberg University have created a therapeutic vaccine that mobilizes the immune system to target cancer cells. The researchers demonstrated that virus peptides combined [...]
Quantitative imaging method reveals how cells rapidly sort and transport lipids
Lipids are difficult to detect with light microscopy. Using a new chemical labeling strategy, a Dresden-based team led by André Nadler at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) and [...]
Ancient DNA reveals cause of world’s first recorded pandemic
Scientists have confirmed that the Justinian Plague, the world’s first recorded pandemic, was caused by Yersinia pestis, the same bacterium behind the Black Death. Dating back some 1,500 years and long described in historical texts but [...]
“AI Is Not Intelligent at All” – Expert Warns of Worldwide Threat to Human Dignity
Opaque AI systems risk undermining human rights and dignity. Global cooperation is needed to ensure protection. The rise of artificial intelligence (AI) has changed how people interact, but it also poses a global risk to human [...]
Nanomotors: Where Are They Now?
First introduced in 2004, nanomotors have steadily advanced from a scientific curiosity to a practical technology with wide-ranging applications. This article explores the key developments, recent innovations, and major uses of nanomotors today. A [...]
Study Finds 95% of Tested Beers Contain Toxic “Forever Chemicals”
Researchers found PFAS in 95% of tested beers, with the highest levels linked to contaminated local water sources. Per- and polyfluoroalkyl substances (PFAS), better known as forever chemicals, are gaining notoriety for their ability [...]
Long COVID Symptoms Are Closer To A Stroke Or Parkinson’s Disease Than Fatigue
When most people get sick with COVID-19 today, they think of it as a brief illness, similar to a cold. However, for a large number of people, the illness doesn't end there. The World [...]
The world’s first AI Hospital, developed in China is transforming healthcare
Artificial Intelligence and its developments have had a revolutionary impact on society, and healthcare is not an exception. China has made massive strides in AI integrated healthcare, and continues to do so as AI [...]
Scientists Rewire Immune Cells To Supercharge Cancer-Fighting Power
Blocking a single protein boosts T cell metabolism and tumor-fighting strength. The discovery could lead to next-generation cancer immunotherapies. Scientists have identified a strategy to greatly enhance the cancer-fighting abilities of the immune system’s [...]