Predicting the molecular cause of autoimmune diseases

Researchers at Cardiff are working to understand how T-cells respond to peptides in order to predict the cause of autoimmune diseases such as diabetes.

The Cardiff T-cell modulation group led by Professor Andy Sewell, covers all areas of T-cell biology, and aims to understand the genetic, biochemical and cellular mechanisms that govern T-cell responses to human disease.

The group is taking a systems approach based on joint work with Warwick Systems Biology Centre (WSB) to predict which T-cell responses cause specific autoimmune diseases.  For the first time, the collaboration has quantified how many different peptides individual T-cells are capable of responding to.

The number of T-cell Receptors (TCRs) in any individual is tiny compared to the enormous amount of potential foreign peptide-MHC that could be encountered. For effective immunity, TCRs need to recognise all possible foreign peptide antigens otherwise gaps appear that pathogens can exploit, and this is when disease occurs. Each T-cell  must be capable of recognising vast numbers of individual peptide sequences thus making them ‘cross-reactive’.

The  study found that T-cell cross reactivity is important as it enables relatively few T-cells to cover all possible foreign peptide antigens to provide comprehensive immune cover. This significant breakthrough is helping us to identify the root cause of all autoimmune diseases, and will help to improve treatment for these diseases.