Progenitor T cells
Migrate from the bone marrow to the thymus. They are attracted to the thymus by a chemotactic factor secreted by thymic epithelial cells. Once in the thymus the pro-T cells express Thy-1 on their surface. The cells are double negative for CD4/CD8.
Two pathways at this point. Those thymocytes that make productive rearrangement of both the gamma and delta chain genes develop into double-negative, CD3+, gamma delta T cells [only 0.5-1.0% of thymocytes in adults]. This cell type is much more numerous early in gestation--->birth.
Alternatively,
The transition from pro-T to pre-T (precursor T) involves the appearance of a structure known as the pre-T receptor. At this time the cells lack CD4 and CD8 (are double negative) but are Thy1 +.
The pre-TCR consists of the CD3 protein and a disulfide-linked heterodimer consisting of the beta chain of the TCR and a 33kDa glycoprotein (gp33), now called pre-T alpha.
(reminiscent of the surrogate light chain of Ig)
The pre-TCR is thought to recognize some ligand within the thymus to transmit a signal through the CD3 complex . Signal transduction through the pre-TCR has the following effects:
1) recognizes that a productive TCR beta chain rearrangement has been made and selects those thymocytes expressing the chain for further expansion and maturation.
2) suppresses further rearrangement of TCR beta chain genes .
3) enhances rearrangement of the TCR alpha chain.
4) Induces developmental progression to the CD4+8+ double state.
Now the thymocytes are referred to as double positive.
Proliferation of these cells occurs. Cells stop proliferation and then the alpha chain genes rearrange. Each of the progeny can theoretically produce a different alpha chain to go with the same beta chain.
An estimated 99% of all thymocytes do not mature and die by apoptosis within the thymus either because they fail to make a productive TCR-gene rearrangement or because they fail to survive thymic selection. Recall that positive selection ensures that the alpha beta TcR s expressed in a given individual will bind to self-MHC [acquisition of MHC restriction]. Negative selection triggers the death of cells bearing a high-affinity receptor for self-MHC alone or self antigen+ self MHC [acquisition of self tolerance].
Double + thymocytes which survive thymic selection develop into either single + CD4+ T cells or single+ CD8 + T cells. These cells migrate out of the thymus.
CD8 + T cells are designated as cytotoxic T cells and they respond to endogenously synthesized peptides + Class I MHC.
CD4+ T cells are designated as helper T cells and they respond to processed exogenous peptides + Class II MHC.
A small population of double negative TcR+ cells can also be detected .
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