title: Transnuclear CD8 T cells specific for the immunodominant epitope Gra6 lower acute-phase Toxoplasma gondii burden.
abstract: We generated a CD8 T-cell receptor (TCR) transnuclear (TN) mouse specific to the Ld-restricted immunodominant epitope of GRA6 from Toxoplasma gondii as a source of cells to facilitate further investigation into the CD8 T-cell-mediated response against this pathogen. The TN T cells bound Ld-Gra6 tetramer and proliferated upon unspecific and peptide-specific stimulation. The TCR beta sequence of the Gra6-specific TN CD8 T cells is identical in its V- and J-region to the TCR-β harboured by a hybridoma line generated in response to Gra6 peptide. Adoptively transferred Gra6 TN CD8 T cells proliferated upon Toxoplasma infection in vivo and exhibited an activated phenotype similar to host CD8 T cells specific to Gra6. The brain of Toxoplasma-infected mice carried Gra6 TN cells already at day 8 post-infection. Both Gra6 TN mice as well as adoptively transferred Gra6 TN cells were able to significantly reduce the parasite burden in the acute phase of Toxoplasma infection. Overall, the Gra6 TN mouse represents a functional tool to study the protective and immunodominant specific CD8 T-cell response to Toxoplasma in both the acute and the chronic phases of infection.
authors.affiliation: Host-Toxoplasma Interaction Laboratory, The Francis Crick Institute, Mill Hill Laboratory, London, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Sanecka
authors.affiliation: Host-Toxoplasma Interaction Laboratory, The Francis Crick Institute, Mill Hill Laboratory, London, UK.
authors.forename: Nagisa
authors.initials: N
authors.lastname: Yoshida
authors.affiliation: Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Stephanie K
authors.initials: SK
authors.lastname: Dougan
authors.affiliation: Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Jackson
authors.affiliation: Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
authors.forename: Nilabh
authors.initials: N
authors.lastname: Shastri
authors.affiliation: Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Hidde
authors.initials: H
authors.lastname: Ploegh
authors.affiliation: INSERM UMR1043, CNRS UMR5282, Université de Toulouse-UPS, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Blanchard
authors.affiliation: Host-Toxoplasma Interaction Laboratory, The Francis Crick Institute, Mill Hill Laboratory, London, UK. eva.frickel@crick.ac.uk.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Frickel
mesh_terms: D000208:Acute Disease; D019264:Adoptive Transfer; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D004195:Disease Models, Animal; D018450:Disease Progression; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006825:Hybridomas; D016056:Immunodominant Epitopes / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D015800:Protozoan Proteins / Q000276:immunology / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D037182:T-Cell Antigen Receptor Specificity; D014122:Toxoplasma / Q000502:physiology*; D014123:Toxoplasmosis / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan; C095047:GRA6 protein, Toxoplasma gondii; D015395:Histocompatibility Antigens Class I; D016056:Immunodominant Epitopes; D015800:Protozoan Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta
keywords: T cells; antigens/peptides/epitopes; parasitic protozoan