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Chapter 8 : Role of Superantigens in Molecular Mimicry and Autoimmunity

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Abstract:

This chapter summarizes various interactive mechanisms by which superantigens may contribute to the development or exacerbation of pathogenic autoimmunity. Superantigens are proteins produced by a number of microbial pathogens, including bacteria and viruses. Cytokines elicited by superantigens are primarily of the Th1 type, some of which have been implicated in the pathogenesis of autoimmunity. The ability of superantigens to activate cells that express class II molecules on their surfaces has led to the suggestion that this may lead to polyclonal activation of B cells and the generation of autoantibodies. Some of the inflammatory cytokines elicited by superantigen including interleukin 12 (IL-12) activate natural killer (NK) cells, which can also contribute to the local destructive inflammatory response. Superantigens, through the action of cytokines, have been shown to induce major histocompatibility complex (MHC) class II expression on a variety of cells and to activate MHC class II-positive endothelial cells. Expression of MHC class II molecules on these nonprofessional antigen- presenting cells (APCs) can lead to aberrant presentation of sequestered self-antigens and the activation of autoreactive cells. The role of superantigens in autoimmunity can be either direct or indirect. Indirectly, superantigens can activate autoreactive T cells that bear Vβ elements recognized by the superantigen, or they can elicit the production of inflammatory cytokines that can exert an adjuvant-like effect, thereby enhancing the recognition of mimicry epitopes shared between microbial and host proteins. The inflammatory response can also change the homing patterns of lymphocytes and cause tissue damage and/or abnormal presentation of sequestered self-antigens.

Citation: Kotb M. 2000. Role of Superantigens in Molecular Mimicry and Autoimmunity, p 95-107. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch8

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Toxic Shock Syndrome Toxin 1
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Major Histocompatibility Complex
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Figure 1

Bridging of T cells and APC: a schematic model of superantigen (SAg) interaction with TCR and class II molecules.

Citation: Kotb M. 2000. Role of Superantigens in Molecular Mimicry and Autoimmunity, p 95-107. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch8
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Image of Figure 2
Figure 2

Mimicry epitopes and sequence homology between SEA and human (Hu) Ii. Alignment data between SEA (UNK_28339310) and the human invariant chain (E27011) show 45% overall homology, with 10% of residues being identical (asterisks), 23.3% being strongly similar (colons), and 13% being weakly similar (periods).

Citation: Kotb M. 2000. Role of Superantigens in Molecular Mimicry and Autoimmunity, p 95-107. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch8
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Image of Figure 3
Figure 3

Mimicry epitopes and sequence homology between SE and non-muscle myosin heavy-chain (HC) gene from . Alignment data between SEA (UNK_28339310) and the myosin heavy chain from (Q10061).

Citation: Kotb M. 2000. Role of Superantigens in Molecular Mimicry and Autoimmunity, p 95-107. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch8
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Image of Figure 4
Figure 4

Mimicry epitopes and sequence homology between SEA and hsp70. Alignment data between SEA (UNK_28339310) and HSP-70 (PF00012) ( ).

Citation: Kotb M. 2000. Role of Superantigens in Molecular Mimicry and Autoimmunity, p 95-107. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch8
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Image of Figure 5
Figure 5

Homology epitopes shared data between SEA (UNK_28339310) and GABA(A) receptor (R) RHO-1 (P24046) ( ) (A) and -crystallin (S-Cryst.) (P18426) ( ) (B).

Citation: Kotb M. 2000. Role of Superantigens in Molecular Mimicry and Autoimmunity, p 95-107. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch8
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