Parasite Stage–Specific Recognition of Endogenous<i>Toxoplasma gondii</i>–Derived CD8<sup>+</sup>T Cell Epitopes

Frickel, Eva‐Maria; Sahoo, Nivedita; Hopp, Johnathan; Gubbels, Marc‐Jan; Craver, Mary Patricia J.; Knoll, Laura J.; Ploegh, Hidde L.; Grotenbreg, Gijsbert M.

doi:10.1086/593019

Cited by 102 publications

(115 citation statements)

References 51 publications

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“…Mouse anti-chicken IFN-g mAbs were kindly given by Dr. Lillehoj (Animal Parasitic Diseases Laboratory, Animal and Natural Resources Institute, U.S. Department of Agriculture) and conjugated to the Pacific Blue dye using a Pacific Blue mAb Labeling Kit (Invitrogen). The fluorescence intensity was measured by the FACSAria II (BD Biosciences) (24,25 (26,27). The data were recorded as stimulation ratio, which is the ratio of cells expressing IFN-g stimulated by EYFP to cells expressing IFN-g without EYFP stimulation.…”

Section: Intracellular Cytokine Stainingmentioning

confidence: 99%

Transgenic Eimeria tenella Expressing Enhanced Yellow Fluorescent Protein Targeted to Different Cellular Compartments Stimulated Dichotomic Immune Responses in Chickens

Huang

Zou

et al. 2011

The Journal of Immunology

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Eimeria tenella, one of the seven species of chicken coccidia, elicits protective immunity against challenge infection with both homologous and heterologous strains. We endeavor to use recombinant E. tenella as a vaccine vehicle for expressing and delivering pathogen Ags and investigate immune responses against these foreign Ags. In this study, two lines of transgenic E. tenella expressing a model Ag, enhanced yellow fluorescent protein (EYFP), targeted to the micronemes and to the cytoplasm of the recombinant parasites were constructed to study the impact of Ag compartmentalization on immunogenicity. The MTT assay, intracellular cytokine staining, and real-time PCR were performed to detect the EYFP-specific proliferation and effector functions of splenic lymphocytes of immunized chickens. ELISA was used to measure anti-EYFP IgG and IgA responses. The results showed that both lines of transgenic parasites stimulated EYFP-specific lymphocyte proliferation and IFN-γ expression in CD4 and CD8 T cells, whereas a higher level of Ag-specific lymphocyte proliferation was elicited by the transgenic line expressing microneme-targeted EYFP. Furthermore, this line stimulated stronger IgA response than the one expressing cytoplasm-targeted EYFP after the second immunization. Our findings are encouraging for further investigation of the effect of Ag compartmentalization in transgenic Eimeria on immunogenicity and for the development of a eukaryotic vaccine vector using genetically modified Apicomplexa parasites.

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Section: Intracellular Cytokine Stainingmentioning

confidence: 99%

Transgenic Eimeria tenella Expressing Enhanced Yellow Fluorescent Protein Targeted to Different Cellular Compartments Stimulated Dichotomic Immune Responses in Chickens

Huang

Zou

et al. 2011

The Journal of Immunology

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“…This approach has been used to examine CD8 T cell responses to T. gondii, leading to the identification of a number of endogenous CD8 antigens (4,7,16,40,62). Most strikingly, mice possessing the MHC-I molecule L d mount an immunodominant response to the HF10 decapeptide derived from the T. gondii protein GRA6 (4).…”

mentioning

confidence: 99%

The Toxoplasma gondii Peptide AS15 Elicits CD4 T Cells That Can Control Parasite Burden

et al. 2012

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ABSTRACTThe apicomplexan parasiteToxoplasma gondiican cause severe disease in immunocompromised individuals. Previous studies in mice have focused largely on CD8+T cells, and the role of CD4 T cells is relatively unexplored. Here, we show that immunization of the C57BL/6 strain of mice, in which the immunodominant CD8 T cell response to the parasite dense-granule protein GRA6 cannot be generated, leads to a prominent CD4 T cell response. To identify the CD4 T cell-stimulating antigens, we generated aT. gondii-specific,lacZ-inducible, CD4 T cell hybridoma and used it as a probe to screen aT. gondiicDNA library. We isolated a cDNA encoding a protein of unknown function that we call CD4Ag28m and identified the minimal peptide, AS15, which was presented by major histocompatibility complex (MHC) class II molecules to the CD4 T cells. Immunization of mice with the AS15 peptide provided significant protection against subsequent parasite challenge, resulting in a lower parasite burden in the brain. Our findings identify the first CD4 T cell-stimulating peptide that can confer protection against toxoplasmosis and provide an important tool for the study of CD4 T cell responses and the design of effective vaccines against the parasite.

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“…human MHC class I HLA-A1, -A2, -A3, -A11 and -B7, [8][9][10] . In subsequent work, this technology has proven useful for the identification of human and murine T cell epitopes in Chlamydia, 11 murine gamma herpes virus, 12 Toxoplasma gondii 13 and melanoma-associated antigens (ref 10 and Reker-Hadrup et al…”

Section: Introductionmentioning

confidence: 99%

Class I Major Histocompatibility Complexes Loaded by a Periodate Trigger

et al. 2009

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Class I major histocompatibility complexes (MHC) present peptide ligands on the cell surface for recognition by appropriate cytotoxic T cells. The unstable nature of unliganded MHC necessitates the production of recombinant class I complexes through in vitro refolding reactions in the presence of an added excess of peptides. This strategy is not amenable to high-throughput production of vast collections of class I complexes. To address this issue, we recently designed photocaged MHC ligands that can be cleaved by a UV light trigger in the MHC bound state under conditions that do not affect the integrity of the MHC structure.The results obtained with photocaged MHC ligands demonstrate that conditional MHC ligands can form a generally applicable concept for the creation of defined peptide-MHC complexes. However, the use of UV exposure to mediate ligand exchange is unsuited for a number of applications, due to the lack of UV penetration through cell culture systems and due to the transfer of heat upon UV irradiation which can induce evaporation. To overcome these limitations, here, we provide proof-of-concept for the generation of defined peptide-MHC complexes by chemical trigger-induced ligand exchange. The crystal structure of the MHC complex with the novel chemosensitive ligand, showcases that the ligand occupied the expected site binding site, in a conformation where the hydroxyl groups should be reactive to periodate. We proceed to validate this technology by producing peptide-MHC complexes that can be used for T cell detection. The methodology that we describe here should allow loading of MHC complexes with defined peptides in cell culture devices, thereby permitting antigen-specific T cell expansion and purification for cell therapy. In addition, this technology will be useful to develop miniaturized assay systems for performing high-throughput screens for natural and unnatural MHC ligands.3

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Parasite Stage–Specific Recognition of EndogenousToxoplasma gondii–Derived CD8⁺T Cell Epitopes

Cited by 102 publications

References 51 publications

Transgenic Eimeria tenella Expressing Enhanced Yellow Fluorescent Protein Targeted to Different Cellular Compartments Stimulated Dichotomic Immune Responses in Chickens

Transgenic Eimeria tenella Expressing Enhanced Yellow Fluorescent Protein Targeted to Different Cellular Compartments Stimulated Dichotomic Immune Responses in Chickens

The Toxoplasma gondii Peptide AS15 Elicits CD4 T Cells That Can Control Parasite Burden

Class I Major Histocompatibility Complexes Loaded by a Periodate Trigger

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Parasite Stage–Specific Recognition of EndogenousToxoplasma gondii–Derived CD8+T Cell Epitopes

Cited by 102 publications

References 51 publications

Transgenic Eimeria tenella Expressing Enhanced Yellow Fluorescent Protein Targeted to Different Cellular Compartments Stimulated Dichotomic Immune Responses in Chickens

Transgenic Eimeria tenella Expressing Enhanced Yellow Fluorescent Protein Targeted to Different Cellular Compartments Stimulated Dichotomic Immune Responses in Chickens

The Toxoplasma gondii Peptide AS15 Elicits CD4 T Cells That Can Control Parasite Burden

Class I Major Histocompatibility Complexes Loaded by a Periodate Trigger

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Parasite Stage–Specific Recognition of EndogenousToxoplasma gondii–Derived CD8⁺T Cell Epitopes