T Cells

T-Cell Activation

There are two classes of T cells; T helper cells (CD4⁺) and cytotoxic T cells (CD8⁺). Table 1 summarizes the reliance of T-cell responses on the dose, localization, and duration of presence of antigen. T-cell stimulation via the TCR, accessory molecules and adhesion molecules results in the activation

Table 1 Dependence of T-Cell Response on Antigen Localization, Amount and Duration of Presence

of various tyrosine kinases (Fig. 1) and mediates stringent and differential regulation of several signaling steps. T-cell induction and activation result from the activation of two signals. In addition to TCR activation (signal 1 = antigen), a costimulatory signal (signal 2) is usually required. Important cost­imulatory signals are delivered by the binding of B7 (B7.1 and B7.2) proteins (present on the APC or B cell) to ligands on the Tcells (CD28 protein, CTLA-4), or by CD40-CD40 ligand interactions. T-cell expansion is also enhanced by 1L-2.

Fig. 1 Regulation of T-cell activation is controlled by multiple signals, including costimulatory signals (Signal 2). Stimulation of the T cell via the T-cell receptor (TCR; Signal 1) activates a tyrosine kinase, which in turn activates phospholipase C (PLC). PLC splits phosphatidylinositol bisphosphate (PIP₂) into inositol trispho- sphate (IP₃) and diacyl glycerol (DAG). IP₃ releases Ca²+ from intracellular depots, whilst DAG activates protein kinase C (PKC). Together, Ca²+ and PKC induce and activate the phosphoproteins required for IL-2 gene transcription within the cell nucleus. Stimulation of a T cell via the TCR alone results in production of only very small amounts of IL-2. Increased IL-2 production often requires additional sig­nals (costimulation, e.g., via CD28). Costimulation via CD28 activates tyrosine ki­nases, which both sustain the transcription process and ensure post-transcriptional stabilization of IL-2 mRNA. Immunosuppressive substances (in red letters) include cytostatic drugs, anti-TCR, anti-CD3, anti-CD28 (CTLA4), anti-CD40, cyclosporine A and FK506 (which interferes with immunophilin-calcineurin binding, thus reduc­ing IL-2 production), and rapamycin (which binds to, and blocks, immunophilin and hardly reduces IL-2 at all). Anti-interleukins (especially anti-IL-2, or a combina­tion of anti-IL-2 receptor and anti-IL-15) block T-cell proliferation.

T-Cell Activation by Superantigens

In association with MHC class 11 molecules, a number of bacterial and possibly viral products can efficiently stimulate a large repertoire of CD4+ T cells at one time. This is often mediated by the binding of the bacterial or viral product to the constant segment of certain VP chains (and possibly Va chains) with a low level of specificity. Superantigens are categorized as either exogenous or endogenous. Exogenous superantigens mainly include bacterial toxins (staphylococcus enterotoxin types A-E [SEA, SEB, etc.]), toxic shock syndrome toxin (TSST), toxins from Streptococcus pyogenes, and certain retroviruses. Endogenous superantigens are derived from components of certain retroviruses found in mice, and which display superantigen-like be­havior (e.g., murine mammary tumor virus, MMTV). The function of super­antigens during T cell activation can be compared to the effect of bacterial lipopolysaccharides on B cells, in that LPS-induced B cell activation is also polyclonal (although it functions by way of the LPS receptors instead of the 1g receptors.

References

Zinkernagel, R. M. (2005). Medical Microbiology. © Thieme.

مواضيع ذات صلة

Cytokines of Innate Immunity

Complement system

Lymphocytes with Limited Diversity

Tumour immunology

دور الغدة الدرقية

عرض الانتجينات الخارقة super antigens

الخلايا العارضة للمستضدات

Mediators of Inflammation and the Interferons

Natural Killer Cells

CD4 + T lymphocytes

Properties of MHC Genes and Proteins

Structure of Class I MHC Molecules