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|Title:||Degradation-resistant protein domains limit host cell processing and immune detection of mycobacteria|
|Authors:||Koh, K.W. |
|Keywords:||Cytotoxic T cells|
|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|
|Appears in Collections:||Staff Publications|
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