On Wednesday, February 6th, 2008 Joost Neijssen will defend his thesis titled “The fate of intracellular peptides and MHC class I antigen presentation” in order to obtain the doctorate degree from the Leiden University. His promoter is Professor Jacques Neefjes.
The thesis defence is open to the public and will take place in the Lokhorst kerk in Leiden, at 15.00 hours.
His thesis deals with the degradation of intracellular proteins by the proteasome. The resulting protein fragments (peptides) can be regarded as waste, but it is clear that peptides play an important role in several processes, like the immune response. Peptides are destroyed very rapidly and irrespectively of their amino acid sequence. A peptide's length appeared to be important as the half-life increases when additional amino acids are present at the amino-terminus. As exception dibasic N-terminal peptides appeared to be more stable than other peptides, resulting in overrepresentation by HLA-B27 molecules that preferably bind dibasic N-terminal peptides.
Cross-presentation of peptides from infected cells by professional antigen presenting cells (APC) is crucial for a proper immune response because they express the required co-stimulatory molecules. However, the exact mode of antigen transfer is largely unknown, and we describe a novel pathway for cross-presentation, by passive diffusion of peptides through gap junctions from infected cells to APCs. Apoptosis-derived antigens have been shown to be a major source of cross-presented antigens. Peptides from apoptotic cells can be presented by the cell itself, or transferred to healthy neighboring cells and be presented by MHC class I molecules of these cells, thereby facilitating cross-presentation, through gap junction mediated intercellular peptide transfer.
Proposition 11 which accompanies the thesis states: Zolang Blueband niet op de dopinglijst van het WADA staat, blijven wielrenners gewoon met boter op hun hoofd rijden.