Hannah Meyer, a Cold Spring Harbor Laboratory Fellow, and colleagues have published a paper in Nature Communications on how the human thymus synthesizes a list of healthy proteins that T cells should not attack. Her team identified, for the first time, the RNA molecules used to create this list that protects healthy tissue from T cells.
Their discovery may help identify key differences between efficient and flawed immune systems, and lead to improved autoimmune disorder treatments.
The development of central T cell tolerance in the thymus is mediated by the presentation of peripheral self-epitopes by medullary thymic epithelial cells (mTECs). This promiscuous gene expression (pGE) drives mTEC transcriptomic diversity, with non-canonical transcript initiation, alternative splicing, and expression of endogenous retroelements (EREs) representing significant but understudied contributors.
By high-throughput 5 cap and RNA sequencing, we map the expression of genome-wide transcripts in immature and mature human mTECs. Both mTEC populations demonstrate high splicing entropy, possibly influenced by the expression of peripheral splicing factors. EREs enriched in long terminal repeat retrotransposons are up-regulated during mTEC maturation, the latter often found near differentially expressed genes.
We provide an interactive public interface for examining mTECtranscriptomic diversity. Our findings therefore aid in the creation of a map of transcriptomic diversity in the healthy human thymus and may ultimately assist in the identification of thoseepitopes that contribute to autoimmunity and immune recognition of tumor antigens.
T cells must be trained to recognize all of the 20,000 different proteins present in the human body. No other organ in the human body produces all of the proteins necessary for their specific organ function.
Which proteins are made in which cells and tissues are usually strictly controlled, according to Meyer. Thymus cells make all of them to ensure that the immune system works correctly.
Meyer examines the thymus for its role in not only preventing autoimmune illnesses, but also in preventing infections and cancer. She hopes that further investigation of the proteins found in the thymus will help other researchers understand and treat these illnesses.
Hannah Meyer's research and how she manages the immune system may be seen in this article How does anyone stay healthy in a world full of germs?