title: Investigation of early T cell activation: analysis of the effect of specific antigen, interleukin 2 and monoclonal antibodies on intracellular free calcium concentration.
abstract: The three mitogenic anti-T3 antibodies, UCHT1, anti-Leu-4 and WT-32, all produce a rapid increase in T cell intracellular Ca2+ ( [Ca2+]i) in all individuals, as measured by quin 2 tetra-acetoxymethyl ester fluorescence. This indicates that the lack of responsiveness of approximately 30% of individuals to UCHT1 in proliferation assays is not due to failure of the antibody to elicit Ca2+ mobilization and that a rise in [Ca2+]i is per se not adequate to induce cell division. Another mitogenic antibody, WT-31, which is directed against the constant portion of the T cell receptor, did not, however, produce a rapid calcium rise in peripheral blood T cells. The clone HA1.7 gave a similar Ca2+ response to UCHT1. WT-31 did not induce a rise in [Ca2+]i, nor did the specific antigen to which the clone responded. Accessory cells may be required to induce Ca2+ mobilization with these ligands. There was no response to IL2, or an antibody (anti-Tac) to the IL2 receptor. In contrast to peripheral blood T cells treatment of HA1.7 with WT-31 led to an enhancement of the calcium response to subsequent UCHT1 addition. Furthermore, cross-linking of WT-31 on the surface of HA1.7 cells did produce a small rise in [Ca2+]i. The IL2-independent malignant T cell line, HUT78, exhibited a calcium response to both UCHT1 and WT-32. Both of these responses occurred without cross-linking. The T cell receptor is closely associated with cell-surface proteins, including the T3 antigen and these studies confirm the importance of the T3 antigen in T cell activation. They also suggest that the relationship between the T cell receptor and the T3 antigen may vary in T cells in different proliferative states.
authors.forename: K
authors.initials: K
authors.lastname: O'Flynn
authors.forename: E D
authors.initials: ED
authors.lastname: Zanders
authors.forename: J R
authors.initials: JR
authors.lastname: Lamb
authors.forename: P C
authors.initials: PC
authors.lastname: Beverley
authors.forename: D L
authors.initials: DL
authors.lastname: Wallace
authors.forename: P E
authors.initials: PE
authors.lastname: Tatham
authors.forename: W J
authors.initials: WJ
authors.lastname: Tax
authors.forename: D C
authors.initials: DC
authors.lastname: Linch
mesh_terms: D000911:Antibodies, Monoclonal / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000276:immunology; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D007700:Kinetics; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D000939:Epitopes; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D002118:Calcium