Please use this identifier to cite or link to this item:
|Title:||Degradation-resistant protein domains limit host cell processing and immune detection of mycobacteria||Authors:||Koh, K.W.
|Keywords:||Cytotoxic T cells
|Issue Date:||2009||Citation:||Koh, K.W., Lehming, N., Seah, G.T. (2009). Degradation-resistant protein domains limit host cell processing and immune detection of mycobacteria. Molecular Immunology 46 (7) : 1312-1318. ScholarBank@NUS Repository. https://doi.org/10.1016/j.molimm.2008.11.008||Abstract:||The Mycobacterium tuberculosis genome reveals a large family of glycine-alanine rich PE-PGRS proteins. Due to similarities with the glycine-alanine rich Epstein-Barr nuclear antigen 1, there has been interest in whether PE-PGRS proteins inhibit cellular processing and presentation via the major histocompatibility complex class I pathway. We investigated whether PE-PGRS proteins were resistant to ubiquitin-proteasome-dependent degradation and CD8+ T cell recognition. Upon transient expression of ubiquitin fusion constructs of either full-length Rv0978cPE-PGRS protein or its PE domain in HeLa cells, the former was markedly less susceptible to proteasomal degradation. When peptides of varying glycine and alanine content from different PE-PGRS proteins were fused to the N-terminus of SIINFEKL peptide, the alanine-rich fusions elicited lower interleukin-2 responses in SIINFEKL-specific CD8+ T cells, with corresponding decrease in lysis of cells presenting such peptides. When CD8+ T cells from Mycobacterium bovis BCG-immunized mice were stimulated with either full-length PE-PGRS protein Rv3812 or its PE domain, the former exhibited a lower level of cytotoxicity against BCG-infected autologous macrophages. These results suggest that mycobacterium PE-PGRS proteins have domains that confer resistance to ubiquitin-proteasome-dependent protein degradation, and the bacteria may have an abundance of such proteins to evade immune detection and killing of mycobacterium-infected cells. © 2008 Elsevier Ltd. All rights reserved.||Source Title:||Molecular Immunology||URI:||http://scholarbank.nus.edu.sg/handle/10635/24664||ISSN:||01615890||DOI:||10.1016/j.molimm.2008.11.008|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Sep 29, 2020
WEB OF SCIENCETM
checked on Sep 29, 2020
checked on Sep 22, 2020
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.