Leiden University Scholarly Publications

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Bakker, A.H. (2009)

MHC ligand generation in T cell-mediated immunity and MHC multimer technologies for T cell detection

Doctoral Thesis
This thesis focuses on the generation of MHC ligands and their use in analyzing T cell immunity, both in mouse and men. It is roughly split into two sections: the first part deals specifically with the rules governing the generation of MHC ligands, while the second part describes technological advances in the use of these MHC ligands to analyze T cell immunity. The first part of this thesis starts with an introduction on antigen presentation, covering both the different mechanisms through which epitopes are generated and the process by which epitopes are presented to T cells. Emphasis lies on the discoveries in this field of the last decade. This introduction is followed by two chapters on the generation of antigenic epitopes. Chapter two describes the analysis of protease activity in the endocytic pathway, while chapter three investigates the antigenic source of epitopes generated during cross-presentation. The second part of this thesis starts with a review on the status of MHC...Show moreThis thesis focuses on the generation of MHC ligands and their use in analyzing T cell immunity, both in mouse and men. It is roughly split into two sections: the first part deals specifically with the rules governing the generation of MHC ligands, while the second part describes technological advances in the use of these MHC ligands to analyze T cell immunity. The first part of this thesis starts with an introduction on antigen presentation, covering both the different mechanisms through which epitopes are generated and the process by which epitopes are presented to T cells. Emphasis lies on the discoveries in this field of the last decade. This introduction is followed by two chapters on the generation of antigenic epitopes. Chapter two describes the analysis of protease activity in the endocytic pathway, while chapter three investigates the antigenic source of epitopes generated during cross-presentation. The second part of this thesis starts with a review on the status of MHC multimer technology as a tool to analyze antigen specific T cell populations. Chapter five then describes a high-throughput approach to generate a vast array of different peptide-MHC complexes for several human MHC alleles, allowing for faster and more complex applications of MHC multimer technology. In the next chapter, the peptide-exchange technology of chapter 5 is used for the development of another novel strategy: multidimensional encoding of peptide-MHC complexes. This chapter describes the development, validation and use of this encoding technique that allows the parallel detection of antigen-specific T cell responses of up to 25 T cell populations in one single sample. Finally, this thesis concludes with a summary and discussion chapter, giving a short overview of the presented data and discussing its relevance in the field of antigen presentation.Show less
MHC Class I
MHC Class II
T cell
Immunity
MHC multimer
Antigen presentation
Flow cytometry
All authors
Bakker, A.H.
Supervisor
Schumacher, T.N.M.
Qualification
Doctor (dr.)
Awarding Institution
Leiden University Medical Center (LUMC), Leiden University
Date
2009-10-29

Funding

Sponsorship
Nederlands Kanker Instituut, Universiteit Leiden, LSBR, Sanquin Reagents, Stichting Melanoom