RAT BASOPHIL LEUKEMIA (RBL) CELLS SENSITIZED WITH LOW-AFFINITY IGE RESPOND TO HIGH VALENCY ANTIGEN

Background The very low concentrations of IgE antibodies in serum make investigations of the affinity of allergen-specific antibodies extrem ely difficult. in the absence of such studies, the fact that low IgE c oncentrations are capable of inducing powerful effector function has e ncouraged the view that IgE antibodies are typically high affinity ant ibodies. Yet the phenomenon of allergic cross-reactivity suggests that lower affinity IgE antibodies may sometimes be of clinical significan ce. Objectives To investigate the effect of antibody affinity upon mas t cell sensitivity in an in vitro model. Methods Rat basophil leukaemi a (RBL) cells were sensitized with one of three monoclonal IgE antibod ies which bind to trinitrophenylated proteins with varying affinity. S erotonin release was measured after challenge of sensitized cells with trinitrophenylated human serum albumin (TNP-HSA). Results Low valency TNP3-HSA failed to stimulate degranulation of RBL cells sensitized wi th SPE-7 anti-DNP IgE, which binds TNP with low affinity. However, upo n challenge with high concentrations (1250 ng/mL) of TNP8-HSA, or as l ittle as 10 ng/ml of highly substituted TNP23-HSA, low levels of degra nulation were seen. A similar relationship between antigen valency and cell sensitivity was seen with cells sensitized with the H-1 epsilon- DNP anti-DNP IgE, which binds with moderate affinity to TNP proteins. Conclusion High valency antigen is capable of activating RBL cells sen sitized with low affinity antibody. This has important implications fo r our understanding of allergic sensitization. It also suggests that t he long-recognized relationship between antigen valency and RBL cell s ensitivity may partly reflect the high functional affinity of cell-bou nd IgE when directed against multivalent antigen.