title: Mechanisms of immune memory. T cell activation and CD3 phosphorylation correlates with Ta1 (CDw26) expression.
abstract: The Ta1 (CDw26) Ag distinguishes a subset of circulating T lymphocytes that is the major population proliferating to recall Ag challenge. Unlike receptors for growth factors such as IL-2 and transferrin, the Ta1 Ag is present on T cell lines and clones irrespective of cell cycle. The appearance of Ta1 on T cells that respond to recall Ag allowed us to investigate activation requirements that may be associated with T cell immune memory. Ta1+ peripheral blood T cells were induced to proliferate by mAb recognizing either the invariant chains of the TCR, or by pairs of mitogenic antibodies directed to the CD2 molecule. In contrast, Ta1- cells were not stimulated by these antibodies. In addition, Ta1-cells did not proliferate maximally after addition of the phorbol ester PMA in combination with the calcium ionophore Ionomycin, suggesting that the intracellular targets of these agents may not be fully active. Anti-CD3-induced elevation of intracellular calcium levels was equivalent in the two subpopulations, suggesting that calcium mobilization mechanisms were intact. In contrast, PMA-induced phosphorylation of TCR CD3 chains was significantly greater in Ta1+ cells as compared to Ta1- T cells. Taken together, our results indicate that Ta1 expression, which is associated with T cell activation and memory, may be causally related to TCR and CD2-mediated activation mechanisms. The PMA inducible TCR phosphorylation in Ta1+ memory cells associated with their increased ability to proliferate after CD3/TCR or CD2 stimulation suggests that intracellular phosphorylation events may be causally associated with T cell immune memory.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
authors.forename: D A
authors.initials: DA
authors.lastname: Hafler
authors.forename: M
authors.initials: M
authors.lastname: Chofflon
authors.forename: D
authors.initials: D
authors.lastname: Benjamin
authors.forename: N H
authors.initials: NH
authors.lastname: Dang
authors.forename: J
authors.initials: J
authors.lastname: Breitmeyer
mesh_terms: D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D000954:Antigens, Surface / Q000032:analysis* / Q000276:immunology; D018801:CD2 Antigens; D017252:CD3 Complex; D002118:Calcium / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000276:immunology; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D018801:CD2 Antigens; D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium