Peptides derived from IgE heavy chain constant region induce profound IgE isotype-specific tolerance.
(BALB/c x SJL)F1 mice, perinatally injected with peptide-N-glyconase F-treated, deglycosylated IgE heavy chain or recombinant IgE heavy chain (CH epsilon 2-CH epsilon 4), were profoundly inhibited in antigen-specific IgE production. There exist minimally two tolerogenic IgE peptides, residing in the CH epsilon 2 and CH epsilon 4 domains. Peptide I, generated by V8 protease, comprises 39 amino acids within CH epsilon 2, beginning at amino acid 103. Peptide E begins at amino acid 312 of the CH epsilon 4 domain and extends through the CH epsilon 4 domain. The total lack of antigen-specific IgE responses in IgE peptide-treated mice was not due to overproduction of interferon-gamma, nor lack of interleukin (IL)-4, as predicted by the Th2/IL-4 paradigm for IgE production. IgE-tolerant mice exhibited comparable levels of circulating anti-IgE antibodies to those of PBS-treated control mice. IgG obtained from sera of both sources failed to inhibit IgE responses in vitro. Moreover, IgE responses of spleen cells from IgE peptides-treated mice were restored by CD4+ T cells from PBS-treated control mice. We hypothesize that regulation of antigen-specific IgE responses is mediated by CD4+ T cells which normally recognize IgE peptides on IgE precursor B cells, and can be rendered tolerant by perinatal IgE peptide treatment.
Wang
Y
Y
Department of Veterinary and Biomedical Sciences, University of Nebraska-Lincoln 68583-0905, USA.
Schmaltz
R
R
Liu
F T
FT
Robertson
M W
MW
Petro
T M
TM
Chen
S S
SS
D000818:Animals; D000918:Antibody Specificity; D005260:Female; D006868:Hydrolysis; D007108:Immune Tolerance / Q000187:drug effects*; D007127:Immunoglobulin Constant Regions / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D007073:Immunoglobulin E / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D007128:Immunoglobulin Fragments / Q000494:pharmacology; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D007132:Immunoglobulin Isotypes / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology*; D010449:Peptide Mapping; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics
D007127:Immunoglobulin Constant Regions; D007128:Immunoglobulin Fragments; D007143:Immunoglobulin Heavy Chains; D007132:Immunoglobulin Isotypes; D010446:Peptide Fragments; D011994:Recombinant Proteins; D007073:Immunoglobulin E