title: Identification of a cross-reactive HLA-DRB1*0301-restricted CD4 T cell response directed against cholesterol-binding cytolysins from two different pathogens.
abstract: 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.
authors.affiliation: Skin Cancer Unit of the German Cancer Research Center (DKFZ), Faculty for Clinical Medicine Mannheim of the University Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Paschen
authors.forename: Mingxia
authors.initials: M
authors.lastname: Song
authors.forename: Simone
authors.initials: S
authors.lastname: Schenk
authors.forename: Jozef
authors.initials: J
authors.lastname: Janda
authors.forename: Xuan Duc
authors.initials: XD
authors.lastname: Nguyen
authors.forename: Wolfram
authors.initials: W
authors.lastname: Osen
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
authors.forename: Gernot
authors.initials: G
authors.lastname: Geginat
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D003016:Clostridium perfringens / Q000276:immunology; D003429:Cross Reactions; D003603:Cytotoxins / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology*; D059811:HLA-DRB1 Chains; D006360:Heat-Shock Proteins / Q000276:immunology; D006460:Hemolysin Proteins / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D003603:Cytotoxins; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; C020452:Clostridium perfringens theta-toxin; D007371:Interferon-gamma; D002784:Cholesterol; C038705:hlyA protein, Listeria monocytogenes