The [173-196] fragment of ovalbumin suppresses ovalbumin-specific rat IgE responses.
Peptides and protein hydrolysates are attractive tools for the induction of tolerance or regulation of targeted B and/or T cell responses. In vivo, peptides are mainly produced by the action of digestive enzymes or following the processing of exogenous antigens by antigen-presenting cells (APCs). In vitro, these molecules are generally produced by enzymatic digestion and chemical hydrolysis of proteins. We investigated the T and B cell determinants of the major food allergen ovalbumin (nOVA) in rat by analyzing (1) the stimulatory effect of nOVA peptides generated by cyanogen bromide (CNBr) cleavage on nOVA-specific T cells, and (2) the potential of CNBr-derived OVA fractions to induce oral tolerance to nOVA. Peptide fractions of the CNBr-hydrolysated OVA were isolated by high-pressure liquid chromatography and tested for their ability to stimulate nOVA-specific T cells isolated from rats parenterally immunized with nOVA. The nOVA fractions containing the stimulatory determinants were then intragastrically administered to rat to test their potential to induce oral tolerance. The hole CNBr hydolysate stimulated proliferation of nOVA-specific T cells. Three out of the five HPLC-purified peptidic fractions were also able to stimulate proliferation and cytokine production by nOVA-specific T cells. A peptide fraction exhibiting a single peak by HPLC contained the 173-196 nOVA segment and stimulated nOVA-specific T cells. This segment also promoted oral tolerance to nOVA and reduced IgE responses. CNBr hydrolysis releases several peptides with stimulatory effect on nOVA-specific T cells including a new nOVA [173-196] T cell determinant which induces oral tolerance to nOVA.
Ben Nasser
Imed
I
Unité 914 Physiologie de la Nutrition et du Comportement Alimentaire, INRA, INA/P-G 16, rue Claude Bernard, 75231 Paris cedex 05, France.
Boyaka
Prosper N
PN
Fennira Ben Aissa
Fatma
F
Jeddi
Moncef
M
Tome
Daniel
D
D000284:Administration, Oral; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003488:Cyanogen Bromide / Q000737:chemistry; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology*; D007376:Interleukin-2 / Q000032:analysis; D007700:Kinetics; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D010047:Ovalbumin / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D010446:Peptide Fragments / Q000276:immunology* / Q000494:pharmacology; D051381:Rats; D011914:Rats, Inbred BN; D017208:Rats, Wistar; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014611:Vaccination
D000596:Amino Acids; D000911:Antibodies, Monoclonal; D018984:Epitopes, T-Lymphocyte; D007376:Interleukin-2; C116337:OX-6 monoclonal antibody; D010446:Peptide Fragments; D007073:Immunoglobulin E; D010047:Ovalbumin; D003488:Cyanogen Bromide