Identification of Salmonella typhimurium genes responsible for interference with peptide presentation on MHC class I molecules

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Identification of Salmonella typhimurium genes responsible for interference with peptide presentation on MHC class I molecules : Deltayej Salmonella mutants induce superior CD8+ T-cell responses. / Qimron, Udi; Madar, Neta; Mittrücker, Hans-Willi; Zilka, Alon; Yosef, Ido; Bloushtain, Noga; Kaufmann, Stefan H E; Rosenshine, Ilan; Apte, Ron N; Porgador, Angel.

in: CELL MICROBIOL, Jahrgang 6, Nr. 11, 01.11.2004, S. 1057-70.

Publikationen: SCORING: Beitrag in Fachzeitschrift/ZeitungSCORING: ZeitschriftenaufsatzForschungBegutachtung

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@article{2007499ed2a74278b2a30697f5647575,
title = "Identification of Salmonella typhimurium genes responsible for interference with peptide presentation on MHC class I molecules: Deltayej Salmonella mutants induce superior CD8+ T-cell responses",
abstract = "Salmonella-derived epitopes are presented on MHC molecules by antigen-presenting cells, and both CD4+ and CD8+ T cells participate in protective immunity to Salmonella. Therefore, mechanisms that allow Salmonella to escape specific immune recognition are likely to have evolved in this bacterial pathogen. To identify Salmonella genes, which potentially interfere with the MHC class I (MHC-I) presentation pathway, Tn10d transposon mutagenesis was performed. More than 3000 mutants, statistically covering half of the Salmonella genome, were individually screened for altered peptide presentation by infected macrophages. Two mutants undergoing enhanced antigen presentation by macrophages were identified, carrying a Tn10d insertion in the yej operon. This phenotype was validated by specific inactivation and complementation experiments. In accordance with their enhanced MHC-I presentation phenotype, we showed that (i) specific CD8+ T cells were elicited at a higher level in mice, in response to immunization with yej mutants compared to their parental strain in two different experimental settings; and (ii) yej mutants were superior vaccine carriers for heterologous antigens compared to the parental strain in a tumour model.",
keywords = "Animals, Antigen Presentation, Bacterial Proteins, CD8-Positive T-Lymphocytes, Cell Line, Female, Histocompatibility Antigens Class I, Macrophages, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Operon, Receptors, Antigen, T-Cell, Salmonella Infections, Animal, Salmonella Vaccines, Salmonella typhimurium, Vaccination",
author = "Udi Qimron and Neta Madar and Hans-Willi Mittr{\"u}cker and Alon Zilka and Ido Yosef and Noga Bloushtain and Kaufmann, {Stefan H E} and Ilan Rosenshine and Apte, {Ron N} and Angel Porgador",
year = "2004",
month = nov,
day = "1",
doi = "10.1111/j.1462-5822.2004.00418.x",
language = "English",
volume = "6",
pages = "1057--70",
journal = "CELL MICROBIOL",
issn = "1462-5814",
publisher = "Wiley-Blackwell",
number = "11",

}

RIS

TY - JOUR

T1 - Identification of Salmonella typhimurium genes responsible for interference with peptide presentation on MHC class I molecules

T2 - Deltayej Salmonella mutants induce superior CD8+ T-cell responses

AU - Qimron, Udi

AU - Madar, Neta

AU - Mittrücker, Hans-Willi

AU - Zilka, Alon

AU - Yosef, Ido

AU - Bloushtain, Noga

AU - Kaufmann, Stefan H E

AU - Rosenshine, Ilan

AU - Apte, Ron N

AU - Porgador, Angel

PY - 2004/11/1

Y1 - 2004/11/1

N2 - Salmonella-derived epitopes are presented on MHC molecules by antigen-presenting cells, and both CD4+ and CD8+ T cells participate in protective immunity to Salmonella. Therefore, mechanisms that allow Salmonella to escape specific immune recognition are likely to have evolved in this bacterial pathogen. To identify Salmonella genes, which potentially interfere with the MHC class I (MHC-I) presentation pathway, Tn10d transposon mutagenesis was performed. More than 3000 mutants, statistically covering half of the Salmonella genome, were individually screened for altered peptide presentation by infected macrophages. Two mutants undergoing enhanced antigen presentation by macrophages were identified, carrying a Tn10d insertion in the yej operon. This phenotype was validated by specific inactivation and complementation experiments. In accordance with their enhanced MHC-I presentation phenotype, we showed that (i) specific CD8+ T cells were elicited at a higher level in mice, in response to immunization with yej mutants compared to their parental strain in two different experimental settings; and (ii) yej mutants were superior vaccine carriers for heterologous antigens compared to the parental strain in a tumour model.

AB - Salmonella-derived epitopes are presented on MHC molecules by antigen-presenting cells, and both CD4+ and CD8+ T cells participate in protective immunity to Salmonella. Therefore, mechanisms that allow Salmonella to escape specific immune recognition are likely to have evolved in this bacterial pathogen. To identify Salmonella genes, which potentially interfere with the MHC class I (MHC-I) presentation pathway, Tn10d transposon mutagenesis was performed. More than 3000 mutants, statistically covering half of the Salmonella genome, were individually screened for altered peptide presentation by infected macrophages. Two mutants undergoing enhanced antigen presentation by macrophages were identified, carrying a Tn10d insertion in the yej operon. This phenotype was validated by specific inactivation and complementation experiments. In accordance with their enhanced MHC-I presentation phenotype, we showed that (i) specific CD8+ T cells were elicited at a higher level in mice, in response to immunization with yej mutants compared to their parental strain in two different experimental settings; and (ii) yej mutants were superior vaccine carriers for heterologous antigens compared to the parental strain in a tumour model.

KW - Animals

KW - Antigen Presentation

KW - Bacterial Proteins

KW - CD8-Positive T-Lymphocytes

KW - Cell Line

KW - Female

KW - Histocompatibility Antigens Class I

KW - Macrophages

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Mutation

KW - Operon

KW - Receptors, Antigen, T-Cell

KW - Salmonella Infections, Animal

KW - Salmonella Vaccines

KW - Salmonella typhimurium

KW - Vaccination

U2 - 10.1111/j.1462-5822.2004.00418.x

DO - 10.1111/j.1462-5822.2004.00418.x

M3 - SCORING: Journal article

C2 - 15469434

VL - 6

SP - 1057

EP - 1070

JO - CELL MICROBIOL

JF - CELL MICROBIOL

SN - 1462-5814

IS - 11

ER -