They are also potent in production of these TRAs via unique process called promiscuous gene expression (PGE)[3] and might serve as their reservoir.
[4] Furthermore, average lifespan of mTECs does not exceed 2–3 days,[5] probably due to only known PGE activator Autoimmune regulator (Aire),[6] which requires for its proper function generation of DNA double strand breaks.
[citation needed] Unidirectional spreading of mTEC-derived TRAs onto additional APCs via antigen transfer increases the probability of encounter between potential autoreactive T cell and its corresponding TRA and therefore enhances processes of central tolerance.
Despite relevance of antigen transfer, seminal study was published, showing mTECs to form fully established central tolerance without support of additional APCs.
[10] Requirement of indirect presentation of some mTEC-derived TRAs in the case of recessive tolerance was perceived also by additional studies which both firstly demonstrated antigen transfer as an instrument that enables this process.
[13][14] Systemic ablation of dendritic cells (DCs) was shown to cause fatal manifestations of autoimmunity[15] which points to their importance in central tolerance.
[16][17] The most efficient subset in TRA presentation and both modes of central tolerance was found to be CD8α+ thymic-derived DCs (tDCs).
Nevertheless, only tDCs and mDCs were observed to utilize transferred TRAs for indirect presentation which led to the processes of central tolerance.