Gubser, Céline. Studies of suppression using monoclonal regulatory T cells and the importance of co-receptor Lck coupling ratios for negative selection. 2015, PhD Thesis, University of Basel, Faculty of Science.
Available under License CC BY-NC (Attribution-NonCommercial).
Official URL: http://edoc.unibas.ch/diss/DissB_11702
In the first part of the thesis we made use of a RagKO TCR transgenic mouse expressing a Foxp3 transgene. This mouse provides a source of monoclonal CD4+, Foxp3+ T cells with a defined specificity. We show that monoclonal B3K506 Tregs are fully functional in vitro and in vivo and clearly require cognate antigen to be suppressive. We further show that the strength of Treg stimulation determines the strength of Treg mediated suppression. Finally we analysed various suppressive mechanisms used by monoclonal Tregs and found that Treg-Tconv proximity is an important parameter, which correlates with effective suppression.
In the second part of the thesis we aimed to understand the molecular mechanism underlying the affinity threshold for negative selection. We quantified the amount of Lck coupled to CD8 or CD4 coreceptors. We found that CD4 co-receptors have higher Lck coupling ratios than do CD8 co-receptors. In addition we determined the absolute numbers of surface molecules (i.e. CD8α, CD4 and CD3ε) on double positive (DP) thymocytes in B6 and MHC- class I restricted, TCR Tg mouse strains. A model, explaining how the TCR measures antigen affinity to initiate a negative selection signal, was generated. Here we show that the affinity threshold for different co-receptors depends on the probability that a peptide-MHC- TCR complex will collide with a co-receptor carrying Lck during the time pMCH binds to the TCR (Stepanek, O. et al. Cell, 2014)
|Advisors:||Palmer, Ed and Finke, Daniela|
|Faculties and Departments:||03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Nephrologie > Exp. Transplantationsimmunologie und Nephrologie (Palmer)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||1 Online-Ressource (83 Seiten)|
|Last Modified:||30 Aug 2016 09:30|
|Deposited On:||30 Aug 2016 09:27|
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