PEPTIDES DERIVED FROM IGE HEAVY-CHAIN CONSTANT-REGION INDUCE PROFOUNDIGE ISOTYPE-SPECIFIC TOLERANCE

(BALB/cxSJL)F1 mice, perinatally injected with peptide-N-glyconase F-t reated, deglycosylated IgE heavy chain or recombinant IgE heavy chain (CH epsilon 2-CH epsilon 4), were profoundly inhibited in antigen-spec ific IgE production. There exist minimally two tolerogenic IgE peptide s, residing in the CH epsilon 2 and CH epsilon 4 domains. Peptide I, g enerated by V8 protease, comprises 39 amino acids within CH epsilon 2, beginning at amino acid 103. Peptide E begins at amino acid 312 of th e CH epsilon 4 domain and extends through the CH epsilon 4 domain. The total lack of antigen-specific IgE responses in IgE peptide-treated m ice was not due to overproduction of interferon-gamma, nor lack of int erleukin (IL)-4, as predicted by the Th2/IL-4 paradigm for IgE product ion. IgE-tolerant mice exhibited comparable levels of circulating from sera of both sources failed to inhibit IgE responses in vitro. Moreov er, IgE responses of spleen cells from IgE peptides-treated mice were restored by CD4(+) T cells from PBS-treated control mice. We hypothesi ze that regulation of antigen-specific IgE responses is mediated by CD 4(-) T cells which normally recognize IgE peptides on IgE precursor B cells, and can be rendered tolerant by perinatal IgE peptide treatment .