The fate of intracellular peptides and MHC class I antigen presentation

Leiden Repository

The fate of intracellular peptides and MHC class I antigen presentation

Type: Doctoral Thesis
Title: The fate of intracellular peptides and MHC class I antigen presentation
Author: Neijssen, Johannes Jacobus
Publisher: Division of Tumor Biology, The Netherlands Cancer Institute, Amsterdam
Faculty of Medicine / Leiden University Medical Center (LUMC), Leiden University
Issue Date: 2008-02-06
Keywords: Antigen presentation
Antigen Processing
MHC Class I
Abstract: Intracellular proteins are degraded by the proteasome. The resulting protein fragments 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 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 bind preferably binds 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. 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.
Description: Promotor: J.J.C. Neefjes
With summary in Dutch
Faculty: LUMC
Citation: Neijssen, J.J., 2008, Doctoral thesis, Leiden University
Sponsor: The Netherlands Cancer Institute, NKI-AvL, KWF Dutch Cancer Society, Nederlandse Vereniging voor Microscopie.

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