Interactions between the Thy-1 and T-cell antigen receptor pathways in the activation of cytotoxic T cells: evidence from synergistic effects, loss variants, and anti-CD8 antibody-mediated inhibition.
The relationship between activation of cytolytic T-lymphocyte (CTL) clones via the T-cell receptor (Ti) or the Thy-1 molecule was investigated. Anti-Ti and anti-Thy-1 monoclonal antibodies (mAb) can activate CTL clones to secrete interferon-gamma (IFN-gamma). Suboptimal doses of anti-Ti and anti-Thy-1 mAb, as well as suboptimal doses of two different anti-Thy-1 mAb, can synergize to activate T-cell clones. The addition of phorbol myristic acetate (PMA), which is not stimulatory by itself, can enhance the synergistic effect of mAb on IFN-gamma production. Although the Ti and Thy-1 molecules were not found associated at the cell surface, the results presented here indicate that these molecules are functionally associated. Use of Ti loss variants of a CTL clone confirms that Thy-1-mediated signaling is not an alternative to, but is dependent on the Ti-mediated activation pathway. Additionally, use of anti-Lyt-2/3 mAb, previously described as interfering with class I MHC-Ti binding and/or activation and, in some cases, with anti-Ti-mediated activation revealed that anti-Thy-1 mAb-mediated activation was also greatly reduced by the presence of Lyt-2/3-specific mAb. Thus the interaction between Thy-1 and Ti might also involve Lyt-2 (Lyt-3) molecules.
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology* / Q000502:physiology*; D000950:Antigens, Ly / Q000276:immunology*; D000954:Antigens, Surface / Q000502:physiology*; D017252:CD3 Complex; D002999:Clone Cells; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018800:Thy-1 Antigens
D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D000954:Antigens, Surface; D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell; D018800:Thy-1 Antigens; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate