T cell development
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11 سال پیش
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T cells or T lymphocytes are a type of lymphocyte (itself a type of white blood cell) that play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells (NK cells), by the presence of a T-cell receptor (TCR) on the cell surface. They do not have antigen-presenting properties (but rather, requiring B cells or NK cells for its antigen-presenting property). They are called T cells because they mature in the thymus.[1] There are several subsets of T cells, each with a distinct function.
Activation of CD4+ T cells occurs through the simultaneous engagement of the T cell receptor and a costimulatory molecule (like CD28, or ICOS) on the T cell by the major histocompatibility complex (MHCII) peptide and costimulatory molecules on the APC. Both are required for production of an effective immune response; in the absence of co-stimulation, T-cell receptor signalling alone results in anergy. The signalling pathways downstream from costimulatory molecules usually engages the PI3K pathway generating PIP3 at the plasma membrane and recruiting PH domain containing signaling molecules like, PDK1 that are essential for the activation of PKCtheta, and eventual IL-2 production.
The first signal is provided by binding of the T cell receptor its cognate peptide presented on MHCII on an antigen presenting cell. MHCII is restricted to so called professional antigen presenting cells, like dendritic cells, B cells and macrophages to name a few. The peptides presented to CD8+ T cells by MHC class I molecules are 8--9 amino acids in length; the peptides presented to CD4+ cells by MHC class II molecules are longer, usually 12--25 amino acids in length,[11] as the ends of the binding cleft of the MHC class II molecule are open.
The second signal comes from co-stimulation, in which surface receptors on the APC are induced by a relatively small number of stimuli, usually products of pathogens, but sometimes breakdown products of cells, such as necrotic-bodies or heat shock proteins. The only co-stimulatory receptor expressed constitutively by naïve T cells is CD28, so co-stimulation for these cells comes from the CD80 and CD86 proteins, which together constitute the B7 protein, (B7.1 and B7.2 respectively) on the APC. Other receptors are expressed upon activation of the T cell, such as OX40 and ICOS, but these largely depend upon CD28 for their expression. The second signal licenses the T cell to respond to an antigen. Without it, the T cell becomes anergic, and it becomes more difficult for it to activate in future. This mechanism prevents inappropriate responses to self, as self-peptides will not usually be presented with suitable co-stimulation.
11 سال پیش
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