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Chapter 12 : Novel Experimental Models for Dissecting Genetic Susceptibility of Superantigen-Mediated Diseases

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Abstract:

The uncontrolled immunological response triggered by microbial superantigens has been implicated in the etiology of numerous human disorders. The observations that superantigens can differentially activate T cells from different individuals suggested that genetic heterogeneity contributes to the clinical phenotype following exposure to superantigens. More recently, the findings that differences in the avidity of HLA molecules to bind superantigens and present them to T cells could dictate the strength and quality of the cytokine response have provided perhaps the strongest evidence about the contribution of the HLA haplotype to susceptibility or resistance to superantigen-induced disorders. The development of HLA class II transgenic murine models that are superantigen sensitive has been a critical step toward understanding the effect of HLA polymorphism on superantigen-mediated disease expression. , which can cause a chronic inflammatory polyarthritis in genetically susceptible strains of rodents, produces a soluble factor designated mitogen (MAM) with superantigenic properties. The generation of transgenic mice expressing human HLA molecules has been an important step toward the creation of in vivo models for investigating the function of disease-associated HLA class II. Genetic susceptibility to autoimmunity in humans and experimental animal models is due to the presence of multiple disease loci. For many common autoimmune diseases little is known about the potential role of superantigens.

Citation: Medina E. 2007. Novel Experimental Models for Dissecting Genetic Susceptibility of Superantigen-Mediated Diseases, p 183-194. In Kotb M, Fraser J (ed), Superantigens. ASM Press, Washington, DC. doi: 10.1128/9781555815844.ch12

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MHC Class II
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Mouse mammary tumor virus
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Central Nervous System Diseases
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Tumor Necrosis Factor alpha
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Tables

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Table 1.

MHC class II-congenic mouse strains

Citation: Medina E. 2007. Novel Experimental Models for Dissecting Genetic Susceptibility of Superantigen-Mediated Diseases, p 183-194. In Kotb M, Fraser J (ed), Superantigens. ASM Press, Washington, DC. doi: 10.1128/9781555815844.ch12

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