Protein-specific cytotoxic T lymphocytes. Recognition of transfectants expressing intracellular, membrane-associated or secreted forms of β-galactosidase

Rammensee, Hans‐Georg; Schild, Hansjörg; Theopold, Ulrich

doi:10.1007/bf02421334

Cited by 58 publications

(35 citation statements)

References 27 publications

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“…CT26.WT, the ␤-gal expressing CT26.CL25, the C3-4 murine BALB͞c hybridoma transduced with lacZ gene, P815 mastocytoma, and EL4 thymoma and their respective lacZ transfectants P13.1 and E22 have been described (17)(18)(19)(20). B-SC-1 cells (CCL26; American Type Culture Collection) and Hela S3…”

Section: Methodsmentioning

confidence: 99%

Antigen expression by dendritic cells correlates with the therapeutic effectiveness of a model recombinant poxvirus tumor vaccine

Bronte

Carroll

Goletz

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

134

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Recombinant poxviruses encoding tumorassociated antigens (TAA) are attractive as candidate cancer vaccines. Their effectiveness, however, will depend upon expression of the TAA in appropriate antigen-presenting cells. We have used a murine model in which the TAA is ␤-galactosidase (␤-gal) and a panel of recombinant vaccinia viruses (rVV) in which ␤-gal was expressed under early or late promoters at levels that varied over 500-fold during productive infections in tissue culture cells. Remarkably, only those rVV employing early promoters were capable of prolonging the survival of mice bearing established tumors expressing the model TAA. Late promoters were ineffective regardless of their determined promoter strength. The best results were obtained when ␤-gal was regulated by a strong early promoter coupled to a strong late promoter. When a variety of cell types were infected with the panel of viruses in vitro, dendritic cells were found to express ␤-gal only under the control of the early promoters even though late promoters were intrinsically more active in other cell types. Furthermore, in a functional assay, dendritic cells infected in vitro with rVV encoding ␤-gal regulated by an early promoter activated ␤-gal-specific cytotoxic T lymphocytes, whereas similar rVV with a late promoter-regulated gene did not. These data indicate that promoter strength per se is not the most critical quality of a recombinant poxvirus-based tumor vaccine and that the use of promoters capable of driving the production of TAA in ''professional'' antigen presenting cells may be crucial.

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Section: Methodsmentioning

confidence: 99%

Antigen expression by dendritic cells correlates with the therapeutic effectiveness of a model recombinant poxvirus tumor vaccine

Bronte

Carroll

Goletz

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

134

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“…0805B CTL specific for g -gal 876-884 [30] are described elsewhere [31] and were restimulated as described above.…”

Section: Cytotoxic T Cellsmentioning

confidence: 99%

Generation of the vesicular stomatitis virus nucleoprotein cytotoxic T lymphocyte epitope requires proteasome-dependent and -independent proteolytic activities

Stoltze

Dick

Deeg³

et al. 1998

Eur. J. Immunol.

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The proteasome is involved in the generation of most of the MHC class I antigenic epitopes. However, it is not known if the proteasome generates the exact cytotoxic T lymphocyte (CTL) epitope or only epitope precursors which require further modification by additional proteases. Digestion of the extended vesicular stomatitis virus nucleoprotein epitope 52-59 (RGYVYQGL) by the 20S proteasome in vitro shows that the proteasome is capable of generating the correct C terminus but not the exact N terminus of the CTL epitope. This finding suggests that proteolytic activity in addition to the proteasome is required for generation of the CTL epitope. By using the proteasome inhibitor lactacystin we were able to confirm this finding in vivo. Lactacystin prevented the processing of N- and C-terminally extended epitopes, whereas the processing of only N-terminally extended epitopes was unaffected. Thus, the proteasome is necessary and sufficient for the generation of the exact C terminus of this CTL epitope, whereas the exact N terminus seems to be generated by a different protease.

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“…The mastocytoma line P815 was cultured in RPMI standard medium and its ␤gal-expressing variant P13.1 in RPMI standard medium supplemented with 0.5 mg/ml G418. The ␤gal-specific CTL clone was maintained in ␣MEM standard medium containing 100 U IL-2/ml by weekly restimulations using 3 ϫ 10 6 irradiated peptide (TPH-PARIGL)-pulsed splenocytes (H2-L d ) (29) and used for experiments after a 7-to 10-day rest as described elsewhere (33). Langerhans cells were prepared and cultured as described previously (34).…”

Section: Cell Linesmentioning

confidence: 99%

“…In view of our only restricted knowledge of T cell epitopes displayed by M3 melanoma cells, we decided to express the model Ag ␤gal in M3 and M3-GM cells. This protein offers the possibility to readily visualize ␤gal-positive tumor cells and contains well-defined T (and B cell) epitopes (29). The availability of a CTL clone specifically recognizing its immunodominant, L d -restricted T cell epitope allowed us to ask whether lymph nodes draining M3-GM-␤gal injection sites contain cells capable of priming a ␤gal-specific immune response and to define their nature.…”

mentioning

confidence: 99%

Granulocyte-Macrophage Colony-Stimulating Factor-Based Melanoma Cell Vaccines Immunize Syngeneic and Allogeneic Recipients via Host Dendritic Cells

Schneeberger

Lührs

Kutil

et al. 2003

The Journal of Immunology

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Subcutaneous injection of GM-CSF-expressing cancer cells into experimental animals results in protective cancer immunity. To delineate the mode of action of such vaccines, we used trinitrophenyl, the antigenic moiety of the contact allergen trinitrochlorobenzene, as surrogate Ag. Trinitrophenyl-derivatized bone marrow-derived dendritic cells were found to elicit a contact hypersensitivity response in syngeneic, but not in allogeneic recipients, compatible with their expected mode of direct Ag presentation. When expressing GM-CSF, haptenized M3 melanoma cells were also able to induce a contact hypersensitivity response but, in contrast to bone marrow-derived dendritic cells, not only in syngeneic but also in allogeneic recipients. This argues for a critical role of host APC. To identify their nature, we introduced the β-galactosidase (βgal) gene into M3-GM cells. Their administration activated βgal-specific, Ld-restricted CTL in syngeneic BALB/c mice. Evaluation of lymph nodes draining M3-GM-βgal injection sites revealed the presence of cells presenting the respective Ld-binding βgal peptide epitope. Based on their capacity to activate βgal-specific CTL, they were identified as being CD11c+ dendritic cells. These experiments provide a rational basis for the use of GM-CSF-based melanoma cell vaccines in an allogeneic setting.

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Protein-specific cytotoxic T lymphocytes. Recognition of transfectants expressing intracellular, membrane-associated or secreted forms of β-galactosidase

Cited by 58 publications

References 27 publications

Antigen expression by dendritic cells correlates with the therapeutic effectiveness of a model recombinant poxvirus tumor vaccine

Antigen expression by dendritic cells correlates with the therapeutic effectiveness of a model recombinant poxvirus tumor vaccine

Generation of the vesicular stomatitis virus nucleoprotein cytotoxic T lymphocyte epitope requires proteasome-dependent and -independent proteolytic activities

Granulocyte-Macrophage Colony-Stimulating Factor-Based Melanoma Cell Vaccines Immunize Syngeneic and Allogeneic Recipients via Host Dendritic Cells

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