Role of the actin cytoskeleton in T cell absorption and internalization of ligands from APC.
A feature of T-APC interaction is that, via either TCR or CD28, T cells can absorb molecules from APC on to the cell surface and then internalize these molecules. Here, using both normal and TCR-transgenic T cells, we investigated the mechanism of T cell absorption of molecules from APC and the role of the cytoskeleton. The results show that although activated T cells could absorb APC molecules in the form of cell fragments, uptake of molecules by resting T cells required direct T-APC interaction. Based on studies with latrunculin B, surface absorption of molecules by resting T cells was crucially dependent upon the actin cytoskeleton for both CD28- and TCR-mediated absorption. Significantly, however, TCR-mediated absorption became strongly resistant to latrunculin B when the concentration of MHC-bound peptide on APC was raised to a high level, implying that the actin cytoskeleton is only important for absorption when the density of receptor/ligand interaction is low. By contrast, in all situations tested, the actin cytoskeleton played a decisive role in controlling T cell internalization of ligands from the cell surface.
Hwang
I
I
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Sprent
J
J
D000042:Absorption / Q000187:drug effects; D000199:Actins / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D018106:CD28 Antigens / Q000502:physiology; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism / Q000502:physiology*; D007399:Interphase / Q000276:immunology; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009842:Oligopeptides / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines
D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018106:CD28 Antigens; D008024:Ligands; D009842:Oligopeptides; D011948:Receptors, Antigen, T-Cell; D013844:Thiazoles; D053778:Thiazolidines; C037068:latrunculin B