What Determines an Antigen‐Specific IgE Isotypic Response?—A Hypothesis

Abstract

Two models to account for an antigen-specific IgE isotypic response are proposed. Both models assume a first-tiered IgE production induced by antigen and IL-4; however, the processed IgE or Ag-IgE immune complexes stimulate T epsilon cells differently in the two models. In Model I, we propose that T epsilon cells express conventional T-cell receptors which recognize IgE isotypic determinants. Model IA proposes that IgE fragments are processed and recognized along with class II MHC molecules, and T epsilon cell preferentially act on antigen-activated IgE-committed B epsilon cells via recognition of processed membrane IgE determinants but not antigens; thus T epsilon cells are in principle capable of modulating non-antigen-specific polyclonal IgE responses. Model IB proposes that IgE function as a class-restriction determinant for nominal antigens analogous to that of class II molecules, and T epsilon cells exert stringent antigen-specific IgE isotypic responses by recognizing nominal antigens restricted to IgE. T epsilon cells thus exert antigen-specific and IgE concerted immunoregulation, and do not participate in modulating polyclonal IgE production. Model II proposes a heterotypic interaction of IgE with a cell interaction receptor (or IgE Fc receptor) on T cells. T epsilon cells modulate antigen-specific IgE isotypic responses via ligation with IgE-antigen immune complexes on B-cell surface; thus, T epsilon cells in principle contribute to polyclonal IgE responses.