Immunodominant, protective response to the parasite Toxoplasma gondii requires antigen processing in the endoplasmic reticulum
The Toxoplasma gondii peptides recognized by protective CD8 + T cells remain uncharacterized. Shastri and colleagues identify an immunodominant T. gondii peptide generated by a mechanism dependent on the endoplasmic reticulum aminopeptidase ERAAP. The parasite Toxoplasma gondii replicates in a speci...
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| Published in | Nature immunology Vol. 9; no. 8; pp. 937 - 944 |
|---|---|
| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
New York
Nature Publishing Group US
01.08.2008
Nature Publishing Group |
| Subjects | |
| Online Access | Get full text |
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| Abstract | The
Toxoplasma gondii
peptides recognized by protective CD8
+
T cells remain uncharacterized. Shastri and colleagues identify an immunodominant
T. gondii
peptide generated by a mechanism dependent on the endoplasmic reticulum aminopeptidase ERAAP.
The parasite
Toxoplasma gondii
replicates in a specialized intracellular vacuole and causes disease in many species. Protection from toxoplasmosis is mediated by CD8
+
T cells, but the
T. gondii
antigens and host genes required for eliciting protective immunity are poorly defined. Here we identified GRA6, a polymorphic protein secreted in the parasitophorous vacuole, as the source of the immunodominant and protective decapeptide HF10 presented by the H-2L
d
major histocompatibility complex class I molecule. Presentation of the HF10–H-2L
d
ligand required proteolysis by ERAAP, the endoplasmic reticulum aminopeptidase associated with antigen processing. Consequently, expansion of protective CD8
+
T cell populations was impaired in
T. gondii
–infected ERAAP-deficient mice, which were more susceptible to toxoplasmosis. Thus, endoplasmic reticulum proteolysis is critical for eliciting protective immunity to a vacuolar parasite. |
|---|---|
| AbstractList | The parasite Toxoplasma gondii replicates in a specialized intracellular vacuole and causes disease in many species. Protection from toxoplasmosis is mediated by CD8 super(+) T cells, but the T. gondii antigens and host genes required for eliciting protective immunity are poorly defined. Here we identified GRA6, a polymorphic protein secreted in the parasitophorous vacuole, as the source of the immunodominant and protective decapeptide HF10 presented by the H-2L super(d) major histocompatibility complex class I molecule. Presentation of the HF10-H-2L super(d) ligand required proteolysis by ERAAP, the endoplasmic reticulum aminopeptidase associated with antigen processing. Consequently, expansion of protective CD8 super(+) T cell populations was impaired in T. gondii-infected ERAAP-deficient mice, which were more susceptible to toxoplasmosis. Thus, endoplasmic reticulum proteolysis is critical for eliciting protective immunity to a vacuolar parasite. The parasite Toxoplasma gondii replicates in a specialized intracellular vacuole and causes disease in many species. Protection from toxoplasmosis is mediated by CD8(+) T cells, but the T. gondii antigens and host genes required for eliciting protective immunity are poorly defined. Here we identified GRA6, a polymorphic protein secreted in the parasitophorous vacuole, as the source of the immunodominant and protective decapeptide HF10 presented by the H-2L(d) major histocompatibility complex class I molecule. Presentation of the HF10-H-2L(d) ligand required proteolysis by ERAAP, the endoplasmic reticulum aminopeptidase associated with antigen processing. Consequently, expansion of protective CD8(+) T cell populations was impaired in T. gondii-infected ERAAP-deficient mice, which were more susceptible to toxoplasmosis. Thus, endoplasmic reticulum proteolysis is critical for eliciting protective immunity to a vacuolar parasite. The Toxoplasma gondii peptides recognized by protective CD8 + T cells remain uncharacterized. Shastri and colleagues identify an immunodominant T. gondii peptide generated by a mechanism dependent on the endoplasmic reticulum aminopeptidase ERAAP. The parasite Toxoplasma gondii replicates in a specialized intracellular vacuole and causes disease in many species. Protection from toxoplasmosis is mediated by CD8 + T cells, but the T. gondii antigens and host genes required for eliciting protective immunity are poorly defined. Here we identified GRA6, a polymorphic protein secreted in the parasitophorous vacuole, as the source of the immunodominant and protective decapeptide HF10 presented by the H-2L d major histocompatibility complex class I molecule. Presentation of the HF10–H-2L d ligand required proteolysis by ERAAP, the endoplasmic reticulum aminopeptidase associated with antigen processing. Consequently, expansion of protective CD8 + T cell populations was impaired in T. gondii –infected ERAAP-deficient mice, which were more susceptible to toxoplasmosis. Thus, endoplasmic reticulum proteolysis is critical for eliciting protective immunity to a vacuolar parasite. The parasite Toxoplasma gondii replicates in a specialized intracellular vacuole and causes disease in many species. Protection from toxoplasmosis is mediated by CD8 + T cells, but the T. gondii antigens and host genes required for eliciting protective immunity are poorly defined. Here we identified GRA6, a polymorphic protein secreted in the parasitophorous vacuole, as the source of the immunodominant and protective decapeptide HF10 presented by the H-2L d major histocompatibility complex class I molecule. Presentation of the HF10–H-2L d ligand required proteolysis by ERAAP, the endoplasmic reticulum aminopeptidase associated with antigen processing. Consequently, expansion of protective CD8 + T cell populations was impaired in T. gondii– infected ERAAP-deficient mice, which were more susceptible to toxoplasmosis. Thus, endoplasmic reticulum proteolysis is critical for eliciting protective immunity to a vacuolar parasite. |
| Audience | Academic |
| Author | Blanchard, Nicolas Robey, Ellen A Cheng, Tiffany Gonzalez, Federico Schaeffer, Marie Shastri, Anjali J Shastri, Nilabh Joncker, Nathalie T |
| Author_xml | – givenname: Nathalie T surname: Joncker fullname: Joncker, Nathalie T organization: Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California – givenname: Marie surname: Schaeffer fullname: Schaeffer, Marie organization: Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California – givenname: Tiffany surname: Cheng fullname: Cheng, Tiffany organization: Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California – givenname: Nilabh surname: Shastri fullname: Shastri, Nilabh organization: Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California – givenname: Federico surname: Gonzalez fullname: Gonzalez, Federico organization: Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California – givenname: Nicolas surname: Blanchard fullname: Blanchard, Nicolas organization: Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California – givenname: Anjali J surname: Shastri fullname: Shastri, Anjali J organization: Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California – givenname: Ellen A surname: Robey fullname: Robey, Ellen A organization: Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California |
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| SSID | ssj0014764 |
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| Snippet | The
Toxoplasma gondii
peptides recognized by protective CD8
+
T cells remain uncharacterized. Shastri and colleagues identify an immunodominant
T. gondii... The parasite Toxoplasma gondii replicates in a specialized intracellular vacuole and causes disease in many species. Protection from toxoplasmosis is mediated... The parasite Toxoplasma gondii replicates in a specialized intracellular vacuole and causes disease in many species. Protection from toxoplasmosis is mediated... |
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| SubjectTerms | Animals Antigen Presentation Antigens, Protozoan - metabolism Biomedical and Life Sciences Biomedicine Endoplasmic Reticulum - immunology Histocompatibility Antigens Class I - immunology Immunology Infectious Diseases Leucyl Aminopeptidase - deficiency Leucyl Aminopeptidase - immunology Leucyl Aminopeptidase - metabolism Life Sciences Mice Parasites Protected species Protozoan Proteins - metabolism Toxoplasma - immunology Toxoplasma - physiology Toxoplasma gondii Toxoplasmosis Toxoplasmosis - immunology Vacuoles - immunology |
| Title | Immunodominant, protective response to the parasite Toxoplasma gondii requires antigen processing in the endoplasmic reticulum |
| URI | http://dx.doi.org/10.1038/ni.1629 https://link.springer.com/article/10.1038/ni.1629 https://www.ncbi.nlm.nih.gov/pubmed/18587399 https://www.proquest.com/docview/222738167 https://search.proquest.com/docview/19480461 https://search.proquest.com/docview/69337170 https://search.proquest.com/docview/839666469 https://hal.science/hal-04707695 https://pubmed.ncbi.nlm.nih.gov/PMC4976627 |
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