Efecto localizado y sistémico de Superantígenos del grupo II. Evaluación de la resistencia al tratamiento convencional
Superantigens (SAgs) are proteins that generate an exacerbated activation of the immune response throughout the stabilization of the interaction between TCR and MHC-II. Differential biological behavior and interaction with chain mV?8.2 has been described for SEG (Fernández 2006, 2007,2011). As Hypot...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica
2020
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_6717 https://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_6717.dir/6717.PDF |
| Aporte de: |
| Sumario: | Superantigens (SAgs) are proteins that generate an exacerbated activation of the immune response throughout the stabilization of the interaction between TCR and MHC-II. Differential biological behavior and interaction with chain mV?8.2 has been described for SEG (Fernández 2006, 2007,2011). As Hypothesis of this Thesis, it was proposed that the new residues characterized in this interaction are responsible for this differential biological activity and that the activation of the TCR would generate resistance to glucocorticoids (GCs). Through in silico, in vitro and in vivo experiments, hot spot residues of the interface were characterized by obtaining single point mutant proteins with lower or zero affinities for mV?8.2. Resistance to GCs was reported for group II SAgs (SEG, SER, SEC3, SSA) and the egc operon (SEI, SEO). The importance of TCR, PI3K and NF?B activation was demonstrated. The effective use of Compound A was reported. The interaction with CD28 and B7 was described for classic SAgs (Arad 2011; Levy 2016), but no interaction by SPR was recorded for SEG with CD28. The modeling of the complexes suggests a potential interaction of SEG with B7.2. The knowledge generated allows the development of therapies and immunomodulators based on modified SAgs. |
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