Superantigens Induce TCell Activation by Binding the TCR and Mhc Ii Simultaneously

Superantigens are viral or bacterial proteins that bind simultaneously to the Vp domain of a T-cell receptor and to the a chain of a class II MHC molecule. Both exogenous and endogenous superantigens have been identified. Crosslinkage of a T-cell receptor and class II MHC molecule by either type of superantigen produces an activating signal that induces T-cell activation and proliferation (Figure 10-16).

Exogenous superantigens are soluble proteins secreted by bacteria. Among them are a variety of exotoxins secreted by gram-positive bacteria, such as staphylococcal enterotoxins, toxic-shock-syndrome toxin, and exfoliative-dermatitis toxin. Each of these exogenous superantigens binds particular Vp sequences in T-cell receptors (Table 10-3) and crosslinks the TCR to a class II MHC molecule.

Endogenous superantigens are cell-membrane proteins encoded by certain viruses that infect mammalian cells. One group, encoded by mouse mammary tumor virus (MTV), can integrate into the DNA of certain inbred mouse strains; after integration, retroviral proteins are expressed on the membrane of the infected cells. These viral proteins, called minor lymphocyte stimulating (Mls) determinants, bind particular Vp sequences in T-cell receptors and crosslink the TCR to a class II MHC molecule. Four Mls superantigens, originating in different MTV strains, have been identified.

Because superantigens bind outside of the TCR antigen-binding cleft, any T cell expressing a particular Vp sequence will be activated by a corresponding superantigen. Hence, the activation is polyclonal and can affect a significant percentage (5% is not unusual) of the total TH population. The massive activations that follow crosslinkage by a superantigen results in overproduction of TH-cell cytokines, leading to systemic toxicity. The food poisoning induced by staphy-

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Anti Cd28 Crosslinking

of anti-CD28. (c) The resulting anergic T cells cannot respond to normal APCs. (d,e) In the presence of normal allogeneic APCs or anti-CD28, both of which produce the co-stimulatory signal 2, T cells are activated by fixed APCs.

Anti-CD28

FIGURE 10-15

Experimental demonstration of clonal anergy versus clonal expansion. (a,b) Only signal 1 is generated when resting Th cells are incubated with glutaraldehyde-fixed antigen-presenting cells (APCs) or with normal APCs in the presence of the Fab portion of anti-CD28. (c) The resulting anergic T cells cannot respond to normal APCs. (d,e) In the presence of normal allogeneic APCs or anti-CD28, both of which produce the co-stimulatory signal 2, T cells are activated by fixed APCs.

lococcal enterotoxins and the toxic shock induced by toxic-shock-syndrome toxin are two examples of the consequences of cytokine overproduction induced by superantigens.

Superantigens can also influence T-cell maturation in the thymus. A superantigen present in the thymus during thymic processing will induce the negative selection of all thymocytes bearing a TCR Vp domain corresponding to the superantigen specificity. Such massive deletion can be caused by exogeneous or endogenous superantigens and is characterized by the absence of all T cells whose receptors possess Vp domains targeted by the superantigen.

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Responses

  • violanda
    Can any antigen influence t cell maturation?
    8 years ago
  • jude
    What effect does superantigen have if found in the thymus?
    8 years ago
  • ELSA
    What chain of the MHC II do superantigens bind?
    7 years ago

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