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
Scientists Discover Hidden Cause of Alzheimer’s Hiding in Plain Sight
Researchers found the PHGDH gene directly causes Alzheimer’s and discovered a drug-like molecule, NCT-503, that may help treat the disease early by targeting the gene’s hidden function. A recent study has revealed that a gene previously [...]
How Brain Cells Talk: Inside the Complex Language of the Human Mind
Introduction The human brain contains nearly 86 billion neurons, constantly exchanging messages like an immense social media network, but neurons do not work alone – glial cells, neurotransmitters, receptors, and other molecules form a vast [...]
Oxford study reveals how COVID-19 vaccines prevent severe illness
A landmark study by scientists at the University of Oxford, has unveiled crucial insights into the way that COVID-19 vaccines mitigate severe illness in those who have been vaccinated. Despite the global success of [...]
Annual blood test could detect cancer earlier and save lives
A single blood test, designed to pick up chemical signals indicative of the presence of many different types of cancer, could potentially thwart progression to advanced disease while the malignancy is still at an early [...]
How the FDA opens the door to risky chemicals in America’s food supply
Lining the shelves of American supermarkets are food products with chemicals linked to health concerns. To a great extent, the FDA allows food companies to determine for themselves whether their ingredients and additives are [...]
Superbug crisis could get worse, killing nearly 40 million people by 2050
The number of lives lost around the world due to infections that are resistant to the medications intended to treat them could increase nearly 70% by 2050, a new study projects, further showing the [...]
How Can Nanomaterials Be Programmed for Different Applications?
Nanomaterials are no longer just small—they are becoming smart. Across fields like medicine, electronics, energy, and materials science, researchers are now programming nanomaterials to behave in intentional, responsive ways. These advanced materials are designed [...]
Microplastics Are Invading Our Arteries, and It Could Be Increasing Your Risk of Stroke
Higher levels of micronanoplastics were found in carotid artery plaque, especially in people with stroke symptoms, suggesting a potential new risk factor. People with plaque buildup in the arteries of their neck have been [...]
Gene-editing therapy shows early success in fighting advanced gastrointestinal cancers
Researchers at the University of Minnesota have completed a first-in-human clinical trial testing a CRISPR/Cas9 gene-editing technique to help the immune system fight advanced gastrointestinal (GI) cancers. The results, recently published in The Lancet Oncology, show encouraging [...]
Engineered extracellular vesicles facilitate delivery of advanced medicines
Graphic abstract of the development of VEDIC and VFIC systems for high efficiency intracellular protein delivery in vitro and in vivo. Credit: Nature Communications (2025). DOI: 10.1038/s41467-025-59377-y. https://www.nature.com/articles/s41467-025-59377-y Researchers at Karolinska Institutet have developed a technique [...]
Brain-computer interface allows paralyzed users to customize their sense of touch
University of Pittsburgh School of Medicine scientists are one step closer to developing a brain-computer interface, or BCI, that allows people with tetraplegia to restore their lost sense of touch. While exploring a digitally [...]
Scientists Flip a Gut Virus “Kill Switch” – Expose a Hidden Threat in Antibiotic Treatment
Scientists have long known that bacteriophages, viruses that infect bacteria, live in our gut, but exactly what they do has remained elusive. Researchers developed a clever mouse model that can temporarily eliminate these phages [...]
Enhanced Antibacterial Polylactic Acid-Curcumin Nanofibers for Wound Dressing
Background Wound healing is a complex physiological process that can be compromised by infection and impaired tissue regeneration. Conventional dressings, typically made from natural fibers such as cotton or linen, offer limited functionality. Nanofiber [...]
Global Nanomaterial Regulation: A Country-by-Country Comparison
Nanomaterials are materials with at least one dimension smaller than 100 nanometres (about 100,000 times thinner than a human hair). Because of their tiny size, they have unique properties that can be useful in [...]
Pandemic Potential: Scientists Discover 3 Hotspots of Deadly Emerging Disease in the US
Virginia Tech researchers discovered six new rodent carriers of hantavirus and identified U.S. hotspots, highlighting the virus’s adaptability and the impact of climate and ecology on its spread. Hantavirus recently drew public attention following reports [...]
Studies detail high rates of long COVID among healthcare, dental workers
Researchers have estimated approximately 8% of Americas have ever experienced long COVID, or lasting symptoms, following an acute COVID-19 infection. Now two recent international studies suggest that the percentage is much higher among healthcare workers [...]
