Transnuclear CD8 T cells specific for the immunodominant epitope Gra6 lower acute‐phase Toxoplasma gondii burden. Issue 3 (17th August 2016)

• Record Type: Journal Article
• Authors: Sanecka, Anna; Yoshida, Nagisa; Dougan, Stephanie K.; Jackson, John; Shastri, Nilabh; Ploegh, Hidde; Blanchard, Nicolas; Frickel, Eva‐Maria
• Is Part Of: Immunology. Volume 149:Issue 3(2016)
• Page Start: 270
• Page End: 279
• Publication Date: 2016-08-17
• Subjects: antigens/peptides/epitopes -- parasitic protozoan -- T cells; Immunology -- Periodicals
• DOI: 10.1111/imm.12643
• Languages: English
• ISSNs: 0019-2805

Abstract

Abstract : Somatic cell nuclear transfer was used to generate a transnuclear (TN) Toxoplasma epitope‐specific CD8 T‐cell mouse. The CD8 T‐cell epitope recognized is the immunodominant peptide from the dense granule protein Gra6 of the parasite. Gra6 TN CD8 T cells are fully functional and lower the parasite load of an acute‐phase Toxoplasma infection. Summary: We generated a CD8 T‐cell receptor (TCR) transnuclear (TN) mouse specific to the L d ‐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 L d ‐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.