Medullary thymic epithelial cells
mTECs possess the ability to deal with these autoreactive clones via mediation of the processes of central tolerance, namely clonal deletion or T regulatory cells selection, respectively.
In 1989, two scientific groups came up with the hypothesis that the thymus expresses genes which are in the periphery, strictly expressed by specific tissues (e.g.: Insulin produced by β cells of the pancreas) to subsequently present these so-called "tissue-restricted antigens" (TRAs) from almost all parts of the body to developing T cells in order to test which TCRs recognize self-tissues and can be therefore harmful to the body.
[1] It was found, after more than a decade, that this phenomenon is managed specifically by mTECs in the thymus and was named Promiscuous gene expression (PGE).
[4] Aire recognizes target genes of TRAs via specific methylation marks[5][6] and requires about 50 partner molecules for activation of their expression.
Dysfunction of murine Aire gene results in comparable scenario and therefore mouse is used as the model organism for investigation of APECED.
[14] However, more recent studies discovered stable co-expression patterns between TRA genes which are localized in close proximity, suggesting "order in this stochastic process".
[18] The rest starts to express CCR7, which is a receptor for mTEC-generated chemokine CCL21, and migrate after concentration gradient to the thymic medulla to encounter mTECs.
They also express high levels of MHC II and costimulatory molecules CD80/CD86 and rank among efficient antigen-presenting cells (APCs).
[20] Thus, mTECs are capable to present self-generated TRAs on their MHC molecules to select potential autoreactive T cells.
[17] Furthermore, it was also revealed that specific TRAs skew autoreactive T cells into TRegs with much higher efficiency than they do in the case of clonal deletion.
[29] In contrast, another seminal study reveals that mTECs itself suffice to establish both recessive and dominant tolerance without help of additional APCs.
