A previously unknown immune regulatory mechanism involving antibodies that can selectively suppress the activity of T cells has been identified by a multi-institutional research team led by Osaka University. The findings were published in the journal Nature Communications.
Background
The immune system relies on T cells to respond to antigens presented on other cells. In autoimmune diseases, T cells mistakenly identify healthy cells as threats and attack them. Treatment of these conditions involves balancing the need to suppress this harmful immune activity with maintaining protective immunity.
Key Discovery
The study describes an antibody termed an "immune-induced TCR-like antibody" (iTab). Researchers found that iTabs are produced naturally during immune responses in mice. These antibodies function by mimicking a T cell receptor and binding to MHC class II molecules on antigen-presenting cells. This binding prevents T cells from recognizing specific antigens and initiating an immune response.
Experimental Findings
The researchers observed that when antigens included additional flanking regions at the ends of proteins, the immune system generated iTabs that bound to them, blocking T cell recognition.
In a mouse model of an autoimmune disease similar to multiple sclerosis:
- Treatment with iTabs reduced disease severity.
- Treatment with iTabs delayed disease onset.
- Vaccination with peptides designed to induce iTab production also provided protection against the disease.
Potential Applications
The researchers proposed several potential applications based on the findings:
- Therapies that promote iTab production could treat conditions driven by overactive T cells while preserving other immune functions. This approach differs from current immunosuppressants, which suppress the entire immune system.
- Conversely, designing vaccines to avoid inducing iTabs might increase vaccine effectiveness.