Sampling of complementing self-antigen pools by thymic stromal cells maximizes the scope of central T cell tolerance

Autophagy in thymic epithelium shapes the T-cell repertoire and is essential for tolerance

“…These findings may shed light on the observed different antigen presentation characteristics of mTEC-like cell lines [135][136][137] and in situ antigen presentation features of mTEC 49,244 .…”

“…Additionally, Kyewski lab went on to show that the expression of a particular TSA is not found in every single mTEC, but it is rather restricted to 1-3% of total mTEC population, suggesting that it is all mTEC together that collectively build up a mosaic of the peripheral self in the thymus ("immunological homunculus") 47,49 . MTEC appear to be a highly heterogenous group of cells, not only with the respect to the TSA profile that a particular mTEC expresses, but also based on surface expression levels of molecules involved in antigen presenting, i.e., MHC class II and CD80 50,51 .…”

“…The deletion potential of mTEC has been described in a system where the expression of transgenic human C-reactive protein (hCRP) was limited to 1-3% of mTEC. Using TCR transgenic animals specific for hCRP (Dep TCR transgenic) the authors documented that mTEC are able to autonomously delete hCRP specific thymocytes when the antigen is endogenously expressed 49 Studies discussed above imply that the medulla plays an indispensable role in central tolerance, but the exact contribution of the cortex in tolerance induction is still a matter of debate. First reports on negative selection in TCR transgenic systems, where the fate of T cells specific for either endogenous antigen or an antigen expressed as a transgene has been followed, revealed that the self-reactive T cells are eliminated from the repertoire at the early stages of development, i.e., at the DN or DP stages 29,[67][68][69] .…”

“…Still, one has to keep in mind that the sensitivity of the techniques used for MHC class II ligandome analyses might not allow for detection of low abundance peptides that add to the diversity of a MHCII/p repertoire. Intriguingly, while DC are highly proficient in sampling and presenting the extracellular milieu to developing T cells, the capacity of cTEC and mTEC to capture and/or process extracellular antigens has proven to be very low 49,133,134 . Thus, ex vivo isolated DC from mice intravenously injected with myoglobin efficiently presented the antigen to a specific T cell hybridoma, but only weak stimulation has been observed when cTEC and mTEC were used as APC.…”

Ovarian autoimmune disease: clinical concepts and animal models

“…63,64 Notably, when thymic expression of tissuerestricted antigens was examined in situ, proteins and transcripts were found to be distributed sparsely among medullary thymic epithelial cells (mTECs). 65 Further studies were carried out on purified and sorted mTEC from mouse, and then human thymus, using targeted RT-PCR as well as microarray analyses. Remarkably, the list of thymus-expressed tissuerestricted antigens was expanded to include tissues representing …”