title: CD8(+) T cells from mice transnuclear for a TCR that recognizes a single H-2K(b)-restricted MHV68 epitope derived from gB-ORF8 help control infection.
abstract: To study the CD8(+) T cell response against a mouse γ-herpes virus, we generated K(b)-MHV-68-ORF8(604-612)RAG(-/-) CD8(+) T cell receptor transnuclear (TN) mice as a source of virus-specific CD8(+) T cells. K(b)-ORF8-Tet(+) CD8(+) T cells, expanded in the course of a resolving MHV-68 infection, served as a source of nucleus donors. Various in vivo and ex vivo assay criteria demonstrated the fine specificity and functionality of TN cells. TN cells proliferated extensively in response to viral infection, helped control viral burden, and exhibited a phenotype similar to that of endogenous K(b)-ORF8-Tet(+) cells. When compared to OT-1 cells, TN cells displayed distinct properties in response to lymphopenia and cognate antigen stimulation, which may be attributable to the affinity of the TCR expressed by the TN cells. The availability of MHV-68-specific CD8(+) TCR TN mice provides a new tool for investigating aspects of host-pathogen interactions unique to γ-herpes viruses.
authors: Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA.
authors: Sharvan
authors: S
authors: Sehrawat
authors: Oktay
authors: O
authors: Kirak
authors: Paul-Albert
authors: PA
authors: Koenig
authors: Marisa K
authors: MK
authors: Isaacson
authors: Sofia
authors: S
authors: Marques
authors: Gunes
authors: G
authors: Bozkurt
authors: J Pedro
authors: JP
authors: Simas
authors: Rudolph
authors: R
authors: Jaenisch
authors: Hidde L
authors: HL
authors: Ploegh
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D000939:Epitopes / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006183:H-2 Antigens / Q000378:metabolism*; D006566:Herpesviridae Infections / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D018144:Rhadinovirus / Q000378:metabolism*; D014412:Tumor Virus Infections / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D019562:Viral Load / Q000502:physiology; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D000939:Epitopes; D006023:Glycoproteins; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D018398:Homeodomain Proteins; C113454:K8.1 protein, Human herpesvirus 8; D011948:Receptors, Antigen, T-Cell; D014764:Viral Proteins; C064658:RAG-1 protein