Differences in epitopes recognized by T cells during oral tolerance and priming

Area of Science:

• Immunology
• T cell biology
• Oral tolerance

Background:

• Oral administration of protein antigens usually induces immune tolerance.
• Certain conditions, like cyclophosphamide (CY) pretreatment, can shift oral antigen feeding from tolerance to immunity.
• Sensitized T cells, producing granulocyte-macrophage-colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma), are detectable in both tolerance and immunity.

Purpose of the Study:

• To investigate the recognition of the immunodominant T cell epitope on ovalbumin (OVA) after oral priming and tolerance induction.
• To compare T cell responses to whole OVA and a specific peptide epitope (pOVA323-339) in different immune states.

Main Methods:

• Mice were treated with cyclophosphamide (CY) and ovalbumin (OVA) intragastrically, or orally primed to induce tolerance.
• Subcutaneous injection of OVA with complete Freund's adjuvant (CFA) was used as a control for immunity induction.
• T cell responses were assessed by measuring lymphokine release (GM-CSF) in vitro upon stimulation with OVA or the pOVA323-339 peptide.
• MHC class II restriction of responding T cells was analyzed.

Main Results:

• T cells from CY/OVA-treated mice and mice immunized with OVA/CFA recognized both intact OVA and the pOVA323-339 peptide, releasing GM-CSF.
• T cells from tolerized mice, while responsive to intact OVA in vitro, did not recognize the immunodominant pOVA323-339 peptide.
• The T cells responding in tolerized mice were restricted by MHC class II.

Conclusions:

• Oral tolerance induction involves differential recognition of T cell epitopes compared to oral priming that leads to immunity.
• Tolerized T cells may respond to determinants other than the immunodominant epitope recognized during active immunity.
• These findings highlight the complexity of T cell epitope selection in the context of oral immune responses.