title: Agonistic effects of anti-CD2 and anti-CD16 antibodies on human natural killer killing.
abstract: Two monoclonal antibodies (MoAb), 9-1 (anti-CD2) and 3G8 (anti-CD16), were previously shown to enhance the cytotoxic activity of human natural killer (NK) cells. The present study examined the effect of 9-1 and 3G8 with different effector and target cells to determine whether they activate NK cells through a common mechanism. Analysis of purified lymphocyte subpopulations demonstrated that the CD3+CD16+CD3- NK effector cell population is enhanced by both antibodies, while purified CD2+CD16-CD3+ T cells are not activated by either antibody. Although both antibodies enhance killing of K-562 and Daudi, killing of T-cell lines is enhanced by 9-1 and inhibited by 3G8. In contrast, killing of the promyelocytic cell line, U-937 is inhibited by 9-1 and enhanced by 3G8. On NK-susceptible cells the pattern of enhancement with 3G8, an IgG1 MoAb, is consistent with the pattern of target cell expression of an Fc receptor, FcR II, known to bind IgG1 antibodies. This suggests that 3G8 may cross-link effector and target cells through CD16 on the effectors and FcR II on these targets. This could activate NK killing by a mechanism similar to antibody-dependent cellular cytotoxicity reactions (ADCC) with the MoAb in the reverse orientation. The failure of 3G8 F(ab')2 fragments to enhance NK killing, further supports the reverse ADCC mechanism of enhancement by 3G8. The pattern of enhancement mediated by 9-1, an IgG3 MoAb, is not correlated with any target cell Fc-receptor known to bind IgG3 MoAb. The effect of 9-1 may result, instead, from its binding to the unique 9-1 epitope on the CD2 molecule involved in CD2-mediated T-cell activation, as previously described. Alternative mechanisms, including activation of NK killing by 9-1 mediated cross-linking of CD2 and CD16 on the effector cells, have also been discussed.
authors.affiliation: Department of Immunology, Karolinska Institute, Stockholm, Sweden.
authors.forename: C K
authors.initials: CK
authors.lastname: Uggla
authors.forename: M
authors.initials: M
authors.lastname: Geisberg
authors.forename: M
authors.initials: M
authors.lastname: Jondal
authors.forename: R W
authors.initials: RW
authors.lastname: Knowles
mesh_terms: D000276:Adjuvants, Immunologic / Q000502:physiology*; D000911:Antibodies, Monoclonal / Q000502:physiology*; D000920:Antibody-Dependent Cell Cytotoxicity; D000943:Antigens, Differentiation / Q000032:analysis / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D018801:CD2 Antigens; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D011961:Receptors, Fc / Q000032:analysis / Q000276:immunology*; D017452:Receptors, IgG; D011971:Receptors, Immunologic / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D011961:Receptors, Fc; D017452:Receptors, IgG; D011971:Receptors, Immunologic