The potential of an attenuated Salmonella enterica serovar Typhimurium strain as a prophylactic anti-tumor vaccine against the murine fibrosarcoma WEHI 164 was evaluated. Tumor cells were transfected with the DNA sequence encoding the MHC class I-restricted peptide p60(217-225) from Listeria monocytogenes. BALB/c mice received a single orogastric immunization with Salmonella that translocates a chimeric p60 protein via its type III secretion system.
View Article and Find Full Text PDFDifferences in the cleavage specificities of constitutive proteasomes and immunoproteasomes significantly affect the generation of MHC class I ligands and therefore the activation of CD8-positive T cells. Based on these findings, we investigated whether proteasomal specificity also influences CD8-positive T cells during thymic selection by peptides derived from self proteins. We find that one of the self peptides responsible for positive selection of ovalbumin-specific OT-1 T cells, which is derived from the f-actin capping protein (Cpalpha1), is efficiently generated only by immunoproteasomes.
View Article and Find Full Text PDFSeveral recent studies have demonstrated that T-helper cell-dependent events during the initial priming period are required for the generation of CD8(+) T cell-mediated protective immunity. The underlying mechanisms of this phenomenon have not yet been determined, mostly because of difficulties in studying memory T cells or their precursor populations at early stages during immune responses. We identified IL-7 receptor (CD127) surface expression as a marker for long-living memory T cells, most importantly allowing the distinction between memory and effector T cells early after in vivo priming.
View Article and Find Full Text PDFOur knowledge about the kinetics and dynamics of complex pathogen-specific CD8(+) T cell responses and the in vivo development of CD8(+) memory T cells has increased substantially over the past years; in comparison, relatively little is known about the CD4(+) T cell compartment. We monitored and directly compared the phenotypical changes of pathogen (Listeria monocytogenes)-specific CD8(+) and CD4(+) T cell responses under conditions leading to effective and long-lasting protective immunity. We found that the general kinetics of bacteria-specific CD8(+) and CD4(+) T cells during the effector and post-effector phases are synchronized.
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