Identification of a cross-reactive HLA-DRB1*0301-restricted CD4 T cell response directed against cholesterol-binding cytolysins from two different pathogens

Cholesterol-binding cytolysins constitute an evolutionarily conserved family of pore-forming proteins expressed by different Gram-positive pathogens. Listeriolysin O, one well-characterized member of the cytolysin family, is also known to induce specific CD4 and CD8 T cell responses upon infection o...

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Main Authors: Paschen, Annette (Author) , Song, Mingxia (Author) , Nguyen, Xuan-Duc (Author) , Osen, Wolfram (Author) , Schadendorf, Dirk (Author) , Geginat, Gernot (Author)
Format: Article (Journal)
Language:English
Published: 30 May 2006
In: Microbes and infection
Year: 2006, Volume: 8, Issue: 8, Pages: 2034-2043
ISSN:1769-714X
DOI:10.1016/j.micinf.2006.03.010
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.micinf.2006.03.010
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1286457906001626
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Author Notes:Annette Paschen, Mingxia Song, Simone Schenk, Jozef Janda, Xuan Duc Nguyen, Wolfram Osen, Dirk Schadendorf, Gernot Geginat
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Summary:Cholesterol-binding cytolysins constitute an evolutionarily conserved family of pore-forming proteins expressed by different Gram-positive pathogens. Listeriolysin O, one well-characterized member of the cytolysin family, is also known to induce specific CD4 and CD8 T cell responses upon infection of mice with Listeria monocytogenes. Here we describe an HLA-DRB1*0301-restricted listeriolysin O-derived T cell epitope that is conserved among several members of the cytolysin family. An HLA-DRB1*0301-restricted CD4+T cell line, established from spleen lymphocytes of L. monocytogenes-infected HLA-DRB1*0301-transgenic mice, cross-reacted with a homologous peptide from perfringolysin O, a cytolysin expressed by Clostridium perfringens. Ex vivo analysis of infected mice revealed an even broader cross-reaction of T cells with homologous peptides derived from perfringolysin O, streptolysin O, and cereolysin O. Interestingly, a cross-reactive memory CD4+T cell response against the homologous peptides derived from listeriolysin O and perfringolysin O could also be detected in the blood from healthy HLA-DRB1*0301+ human donors. Remarkably, this response was even present in donors who did not exhibit a memory T cell reactivity against a second, non-conserved HLA-DRB1*0301-restricted LLO-derived CD4 T cell epitope, suggesting that cytolysin-producing bacteria other than L. monocytogenes can stimulate a cross-reactive cytolysin-specific immunity.
Item Description:Gesehen am 09.02.2021
Physical Description:Online Resource
ISSN:1769-714X
DOI:10.1016/j.micinf.2006.03.010