IngentaConnect Identification of Salmonella typhimurium genes responsible for in...

Authors: Udi Qimron¹; Neta Madar¹; Hans-Willi Mittrücker²; Alon Zilka¹; Ido Yosef¹; Noga Bloushtain¹; Stefan H. E. Kaufmann²; Ilan Rosenshine³; Ron N. Apte¹; Angel Porgador¹

Source: Cellular Microbiology, Volume 6, Number 11, November 2004 , pp. 1057-1070(14)

Publisher: Blackwell Publishing

Abstract:

Summary

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.

Document Type: Research article

DOI: 10.1111/j.1462-5822.2004.00418.x

Affiliations: 1: Department of Microbiology and Immunology, Faculty of Health Sciences and the Cancer Research Center, Ben Gurion University of the Negev, 84105 Beer Sheva, Israel. 2: Department of Immunology, Max-Planck-Institute for Infection Biology, 10117 Berlin, Germany. 3: Department of Molecular Genetics and Biotechnology, The Hebrew University-Hadassah Medical School, 91120 Jerusalem, Israel.

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Identification of Salmonella typhimurium genes responsible for interference with peptide presentation on MHC class I molecules: yej Salmonella mutants induce superior CD8+ T-cell responses

Identification of Salmonella typhimurium genes responsible for interference with peptide presentation on MHC class I molecules: yej Salmonella mutants induce superior CD8⁺ T-cell responses