Bioorthogonal protein labelling enables the study of antigen processing of citrullinated and carbamylated auto-antigens
| Autor: | Can Araman, Mikkel H. S. Marqvorsen, René E. M. Toes, Marcel Camps, George M.C. Janssen, Ferry Ossendorp, Clarissa R. Nascimento, Gerard J. P. van Westen, Willemijn van der Wulp, G. J. Mirjam Groenewold, Arieke S. B. Kampstra, Thomas Bakkum, Tyrza van Leeuwen, Antonius P A Janssen, Herman S. Overkleeft, Peter A. van Veelen, Sander I. van Kasteren, Bogdan I. Florea, Linda Pieper Pournara |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Proteolysis
010402 general chemistry 01 natural sciences Biochemistry Genetics and Molecular Biology (miscellaneous) Biochemistry 03 medical and health sciences Immune system Antigen medicine Molecular Biology 030304 developmental biology 0303 health sciences medicine.diagnostic_test biology Chemistry Antigen processing Citrullination Acquired immune system 3. Good health 0104 chemical sciences Cell biology Ovalbumin Chemistry (miscellaneous) biology.protein Bioorthogonal chemistry |
| Zdroj: | RSC Chemical Biology, 2(3), 855-862. Royal Society of Chemistry ({RSC}) Rsc Chemical Biology RSC Chemical Biology, 2(3), 855-862. ROYAL SOC CHEMISTRY RSC Chemical Biology |
| Popis: | Proteolysis is fundamental to many biological processes. In the immune system, it underpins the activation of the adaptive immune response: degradation of antigenic material into short peptides and presentation thereof on major histocompatibility complexes, leads to activation of T-cells. This initiates the adaptive immune response against many pathogens. Studying proteolysis is difficult, as the oft-used polypeptide reporters are susceptible to proteolytic sequestration themselves. Here we present a new approach that allows the imaging of antigen proteolysis throughout the processing pathway in an unbiased manner. By incorporating bioorthogonal functionalities into the protein in place of methionines, antigens can be followed during degradation, whilst leaving reactive sidechains open to templated and non-templated post-translational modifications, such as citrullination and carbamylation. Using this approach, we followed and imaged the post-uptake fate of the commonly used antigen ovalbumin, as well as the post-translationally citrullinated and/or carbamylated auto-antigen vinculin in rheumatoid arthritis, revealing differences in antigen processing and presentation. Click handle-containing antigens can be used to study uptake, processing and presentation by immune cells. |
| Databáze: | OpenAIRE |
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