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, Vol. 6, No. 11, 01.11.2004, p. 1057-70.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -