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Through the action of AIRE, medullary thymic epithelial cells (mTEC) express major proteins from elsewhere in the body (so called "tissue-restricted antigens" - TRA) and T cells that respond to those proteins are eliminated through cell death . Thus AIRE drives negative selection of self-recognizing T cells. [7]
This phenomenon enables generation of self-antigens, so called tissue-restricted antigens (TRAs), which are in the body expressed only by one or few specific tissues (antigens rank among TRAs if they are expressed by less than five tissues from the sixty tested [1]).
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 ...
MHC-restricted antigen recognition, or MHC restriction, refers to the fact that a T cell can interact with a self-major histocompatibility complex molecule and a foreign peptide bound to it, but will only respond to the antigen when it is bound to a particular MHC molecule.
Maturation of mTEC leads to expression of high levels of MHCII, CD80, autoimmune regulator Aire and tissue restricted antigens (TRAs). Expression of Cathepsin L and Cathepsin S is also typical for mTEC, because of participation of these proteases in the negative selection of T cells.
All T cells derive from progenitor cells in the bone marrow, which become committed to their lineage in the thymus.All T cells begin as CD4-CD8-TCR- cells at the DN (double-negative) stage, where an individual cell will rearrange its T cell receptor genes to form a unique, functional molecule, which they, in turn, test against cells in the thymic cortex for a minimal level of interaction with ...
Since its discovery in 2001, [3] AIRE (Autoimmune regulator) has been the main focus of studies of thymic (central) immune tolerance.AIRE induces the expression of many antigens specific to differentiated cells not found in the thymus (termed peripheral tissue antigens or tissue restricted antigens) thus helping to detect and remove T cells that react with these antigens. [4]
Group 1 CD1-restricted T cells express diverse αβ T-cell receptors . They can undergo clonal expansion in the periphery after recognition of stimulatory self-lipids or exogenous lipid antigens derived from bacteria. [2] CD1–restricted T cells produce T H 1, IFN-γ and TNF-α cytokines and are cytolytic.