Immunochemical approaches to monitor and modulate the adaptive immune system

Luimstra, J.J. (2020)

Doctoral Thesis

The two branches of our highly advanced immune system work closely together to detect and eliminate pathological threats. The first line of defense is provided by the innate immune system via detection of pathogenic or tumor cell fragments. Adaptive immune cells, on the other hand, recognize pathogens or malignant cells more specifically by scanning peptides, small protein fragments, presented by MHC molecules on other cells in our body. Specialized white blood cells (cytotoxic or killer T cells) can distinguish self- from non-self-peptides and directly eliminate cells that display signs of infection or mutation.
The work described in this dissertation highlights how adaptive immunity can be used to our advantage, either from a therapeutic or diagnostic perspective. Immunotherapies that induce or promote anti-tumor or anti-viral responses have proven efficacious against infection and cancer. One strategy described is the development of chemically-modified epitopes as peptide vaccines, but small-molecule chemical drugs are also playing an increasing role in the field of cancer immunotherapy.
In addition, monitoring of immune status and response to treatment, as well as mapping of epitopes, can aid diagnosis and design of treatment plans. The second part describes a novel method and application to visualize and monitor cytotoxic T cells.

• MHC class I
• CD8+ T cell staining
• Peptide
• Thermal exchange
• Multimer
• Flow cytometry
• Immunotherapy

• All authors: Luimstra, J.J.
• Supervisor: Ovaa, H.; Neefjes, J.J.C.
• Committee: Borst, J.G.; Elliott, T.J.; Ossendorp, F.A.; Berlin, I.; Kasteren, S.I. van
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden University of Medical Center [LUMC], Leiden University
• Date: 2020-02-12
• ISBN (print): 9789464020366