Thursday, January 24, 2013

T cell Heterogeneity

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T cells are a subset of lymphocytes that play a large role in the primary immune response. These cells exhibit phenotypic and/or functional heterogeneity [1].


Phenotypic heterogeneity arises from the expression of different markers on the cell surface. There are two well-defined subpopulations of T cells, namely T helper (Th) and T cytotoxic (Tc) cells, both of which express one or the other of two membrane glycoprotein molecules CD4 and CD8. T cells that express CD4 i.e. Th can only recognise antigen bound to class II MHC molecules, whereas T cells expressing CD8 (Tc) are restricted to recognition of antigen bound to class I MHC molecule.


The differences in phenotypes of the T cell results in differences in function. Within the T helper cells are two distinct kinds, Th1 and Th cells. Just like all T cells, these mature in the thymus but are only produced when T cells encounter dendritic cells, which present antigen to the TCR. Th1 and Th cells are produced when DC1 and DC types dentritic cells present antigen to the TCR respectively (figure 1). The generation of an immune response both humoral by B cells and cell-mediated by Tc cells (CD8+) depends on the activation of Th cells. Th1 subset produces great amounts of IL- and IFN gamma; cytokines particularly important in cell mediated immunity. The Th subset is very good at providing B cell help by secreting IL-4,-5 and 6. The molecular basis for Th1- and Th-specific gene expression remains to be elucidated. However it has been found that Th cells express the GATA- gene whereas Th1 cells do not [].


The main role of the cytotoxic T cell, as the name suggests, is to kill other cells. The requirement for MHC class I on the target cell means that the Tc cell is very important in recognizing and destroying self-cells that have been altered or infected. The Tc cell must first become activated and mature into a cytotoxic T lymphocyte (CTL). These CTLs express on their surface molecules of a transmenbrane protein called the Fas Ligand. This is useful in ‘killing’ most potential CTL targets as they express Fas (receptor for FasL) on their cell surface.


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The T cell receptor made up of different heterodimers also contributes to phenotypic heterogeneity. The T cell receptors composed of and polypeptide chains can directly recognise antigens in the form of intact proteins or non-peptide compounds while those made up of and recognise antigens bound to MHC molecules. About 5% of peripheral blood T cells bear TCRs, most of which recognise non-peptide phosphorylated antigens []. TCRs and TCRs are both a result of rearranging gene segments. The chain is encoded by V, J and C segments. The chain is encoded by V, D, J and C gene segments. So rearrangement of the TCR and chain gene segments results in VJ joining for the chain and VDJ joining for the chain. Several mechanisms operate during TCR gene rearrangement and thus creating a high degree of diversity among T cell receptors. Figure shows the TCR, which the mature cytotoxic T lymphocytes express and figure compares the TCR and TCR.





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