Cortical thymic epithelial cells

Thymus tissue is compartmentalized into cortex and medulla and each of these two compartments comprises its specific thymic epithelial cell subset.

While cTECs control the functionality of TCRs during the process called positive selection, Medullary thymic epithelial cells (mTECs) that home in the inner part of the thymus- medulla, present on their MHC molecules self-peptides, generated mostly by protein Autoimmune regulator, to eliminate T cells with self-reactive TCRs via processes of central tolerance e.g. negative selection and protect the body against development of autoimmunity.

Enzymatic machinery for MHC I antigen processing and presentation in cTECs involves thymoproteasome, which is defined by the presence of β5t subunit encoded by Psmb11 gene.

[3] MHC II processing and presentation in cTECs took advantage of several proteolytic pathways including cathepsin L, encoded by Ctsl gene.

[20] Ctsl knockout mouse revealed severe reduction in frequency and repertoire of CD4 T cells and impairment of invariant chain degradation.

[23] This process involves engulfment of portion of cytoplasm that contains organelles and vesicles into autophagosome that fuses with late endosomes or lysosomes and its content is chopped to small peptides.

[24] cTECs and mTECs utilize this endogenous pathway for MHC II presentation during selection processes, instead of common loading of exogenous peptides.