CD1d-specific NK1.1+ T cells with a transgenic variant TCR.
The majority of T lymphocytes carrying the NK cell marker NK1.1 (NKT cells) depend on the CD1d molecule for their development and are distinguished by their potent capacity to rapidly secrete cytokines upon activation. A substantial fraction of NKT cells express a restricted TCR repertiore using an invariant TCR Valpha14-Jalpha281 rearrangement and a limited set of TCR Vbeta segments, implying recognition of a limited set of CD1d-associated ligands. A second group of CD1d-reactive T cells use diverse TCR potentially recognizing a larger diversity of ligands presented on CD1d. In TCR-transgenic mice carrying rearranged TCR genes from a CD1d-reactive T cell with the diverse type receptor (using Valpha3. 2/Vbeta9 rearrangements), the majority of T cells expressing the transgenic TCR had the typical phenotype of NKT cells. They expressed NK1.1, CD122, intermediate TCR levels, and markers indicating previous activation and were CD4/CD8 double negative or CD4+. Upon activation in vitro, the cells secreted large amounts of IL-4 and IFN-gamma, a characteristic of NKT cells. In mice lacking CD1d, TCR-transgenic cells with the NKT phenotype were absent. This demonstrates that a CD1d-reactive TCR of the "non-Valpha 14" diverse type can, in a ligand-dependent way, direct development of NK1.1+ T cells expressing expected functional and cell-surface phenotype characteristics.
Sköld
M
M
Department of Cell and Molecular Biology, Lund University, Sweden.
Faizunnessa
N N
NN
Wang
C R
CR
Cardell
S
S
D000818:Animals; D000831:Animals, Newborn / Q000235:genetics / Q000276:immunology; D000941:Antigens / Q000096:biosynthesis*; D018949:Antigens, CD1 / Q000276:immunology* / Q000378:metabolism; D055610:Antigens, CD1d; D000950:Antigens, Ly; D000954:Antigens, Surface; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D019673:Genes, T-Cell Receptor alpha; D019674:Genes, T-Cell Receptor beta; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055651:NK Cell Lectin-Like Receptor Subfamily B; D014176:Protein Biosynthesis; D011506:Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D019076:Transgenes / Q000276:immunology*
D000941:Antigens; D018949:Antigens, CD1; D055610:Antigens, CD1d; D000950:Antigens, Ly; D000954:Antigens, Surface; D018984:Epitopes, T-Lymphocyte; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D008024:Ligands; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta