Activation of human T cell clones and Jurkat cells by cross-linking class I MHC molecules.
Cross-linking class I MHC molecules on human T cell clones by reacting them with various mAb directed at either monomorphic or polymorphic determinants on class I MHC molecules followed by cross-linking with GaMIg stimulated a rise in intracellular free calcium concentration ([Ca2+]i), and induced proliferation and IL-2 production. T cell clones varied in the mean density of class I MHC molecules and the capacity to respond to mAb to class I MHC molecules. However, the functional responses of the clones did not correlate with class I MHC density or the CD4/CD8 phenotype. mAb to polymorphic class I MHC determinants were less able to induce an increase in [Ca2+]i and a functional response in the T cell clones. Additive stimulatory effects were noted when mAb against both HLA-A and HLA-B determinants were employed. Cross-linking class I MHC molecules on Jurkat cells induced a rise by [Ca2+]i and induced IL-2 production upon co-stimulation with PMA. Cross-linking class I MHC molecules on mutant Jurkat cells that expressed diminished levels of CD3 and were unable to produce IL-2 in response to anti-CD3 stimulation triggered both a rise in [Ca2+]i and IL-2 production with PMA co-stimulation. In contrast, cross-linking class I MHC molecules on mutant Jurkat cells that were CD3- stimulated neither a rise in [Ca2+]i nor IL-2 production. The combination of mAb to CD28 or ionomycin and PMA, however, was able to induce IL-2 production by CD3- Jurkat cells. The data demonstrate that cross-linking class I MHC molecules delivers a functionally important signal to T cell clones and Jurkat cells and indicate that class I MHC molecules may function to transduce activation signals to T cells. In addition, the data demonstrate that transmission of an activation signal via class I MHC molecules requires CD3 expression. The data, therefore, support a central role for CD3 in the transduction of activation signals to T cells via class I MHC molecules.
Geppert
T D
TD
Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center, Dallas 75235.
Wacholtz
M C
MC
Patel
S S
SS
Lightfoot
E
E
Lipsky
P E
PE
D000911:Antibodies, Monoclonal / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D003432:Cross-Linking Reagents; D003600:Cytosol / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D000939:Epitopes / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000502:physiology; D008213:Lymphocyte Activation; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate
D000911:Antibodies, Monoclonal; D003432:Cross-Linking Reagents; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D004247:DNA; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium