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01/06/2020

How are T cells selected in the thymus?

How are T cells selected in the thymus?

Lymphoid progenitors which have developed from hematopoietic stem cells in the bone marrow migrate to the thymus to complete their antigen-independent maturation into functional T cells . In the thymus, T cells develop their specific T cell markers, including TCR, CD3, CD4 or CD8, and CD2.

Where does positive selection of T cells occur in the thymus?

In order for mature, antigen-recognizing T cells to develop without being self-reactive and causing autoimmunity, T cells must go through both positive and negative selection. In positive selection, T cells in the thymus that bind moderately to MHC complexes receive survival signals (middle).Dhuʻl-H. 9, 1439 AH

Why is thymic selection needed?

Intrathymic T cell development represents one of the best studied paradigms of mammalian development. Positive and negative selection of immature alphabetaTCR-expressing cells are essential mechanisms for generating mature T cells, committing them to the CD4 and CD8 lineages and avoiding autoimmunity.

Where does T cell selection occur?

The selection of a functional and self-tolerant T cell repertoire is coordinated by multiple selection processes that occur during T cell development in the thymus; including positive selection, negative selection, and agonist selection.

What is thymic selection?

Thymic selection takes place in the thymus and approximately 2% of the original, immature T cells survive this process. Resulting from this selection are populations of T-cell clones, each of which has a potential to recognize, as complexed with MHC, many foreign, i.e., exogenous antigens, but not self antigens.Rab. I 12, 1438 AH

Where does negative selection occur in the thymus?

Unlike the cortex, the thymic medulla is packed with bone marrow (BM)–derived APC and is permeable to circulating self-antigens entering from the bloodstream (14). Thus, the medulla is a likely site for negative selection.

What are positive and negative thymic selections?

A process referred to as positive selection removes cells with TCR conformations that are generally non-responsive to self-peptide–MHC ligands (self-pMHC), and negative selection removes cells that are overly reactive to self-pMHC and pose a threat of autoimmune responses.Rab. II 4, 1435 AH

Why is positive selection important?

Positive selection selects cells which are able to bind MHC class I or II molecules with at least a weak affinity. This eliminates (by a process called “death by neglect”) those T cells which would be non-functional due to an inability to bind MHC.

What is the purpose of negative selection of B and T cells?

Developing B cells are positively selected when the pre-B receptor binds its ligand. (Developing T cells are positively selected for their ability to bind MHC as well as peptide.) Negative selection means that binding to the receptor results in cell death.