Antigen transfer in the thymus
transmission of self-antigens
Antigen transfer in the thymus is the transmission of self-antigens between thymic antigen-presenting cells which contributes to the establishment of T cell central tolerance.
Thymus represents an origin of T cell development and its responsibility is to select functional but also safe T cells which will not attack self tissues. Self-harmful T cells, further referred to as autoreactive T cells, originate in the thymus because of the stochastic process called V(D)J recombination which conducts the generation of T cell receptors (TCRs) and enables their limitless variability. Two processes of central tolerance take place in thymic medulla, namely clonal deletion (recessive tolerance) and T Regulatory cells selection (dominant tolerance) which force autoreactive T cells to apoptosis or skew them into suppressor T regulatory cells (TRegs), respectively, in order to protect body against manifestations of autoimmunity.
These processes are mediated especially by unique subset of stromal cells called Medullary thymic epithelial cells (mTECs) via presentation of Tissue restricted antigens (TRAs) that represent self tissues from almost all parts of the body.
mTECs
mTECs are not only capable to present TRAs as efficient APCs. They are also potent in production of these TRAs via unique process called promiscuous gene expression (PGE) and might serve as their reservoir.
Drawbacks of antigen presentation
mTECs as APCs reveal some drawbacks on population level. Their numbers in thymic medulla reach only 100,000 per 2-week-old thymus. Furthermore, average lifespan of mTECs does not exceed 2–3 days, probably due to only known PGE activator Autoimmune regulator (Aire), which requires for its proper function generation of DNA double strand breaks.
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