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IIG Seminar - A T-Rex tale: antigen-specific suppression by depletion of peptide-MHCII

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Air date: Wednesday, January 8, 2020, 4:30:00 PM
Time displayed is Eastern Time, Washington DC Local
Views: Total views: 595
Category: Immunology
Runtime: 01:07:27
Description: Regulatory T cells (Tregs) are professional suppressors of the immune response, yet their mechanism of action in vivo remains unclear. We compared the morphology and stoichiometry of the interactions of antigen-specific activated T cells and iTregs with antigen-pulsed dendritic cells (DC) and revealed that Tregs interacting with DCs displayed a distinct morphology with finger like membrane protrusions at the DC binding site and uropods at their rear end within three hours of in vitro co-culture. In contrast, we demonstrated that activated T cells maintained their round morphology. Tregs occupied a greater extent of the DC surface than activated T cells consistent with a higher binding avidity. Dynamic intravital two-photon microscopy of adoptively transferred antigen-specific Tregs and activated T cells demonstrated that Tregs displayed a greater volume and duration of contact with antigen-pulsed DCs compared to that of activated T cells. Subsequent to their high-avidity interactions with DCs, antigen-specific Tregs captured peptide-MHC Class II (pMHCII) complexes from DC surface reducing the amount of antigen presented on DC. Reduced antigen presentation was not due to a global suppression of the DCs’ ability to present antigen as antigen specific Tregs only captured their cognate pMHCII from DCs, without interfering the antigen presentation machinery of the DCs, that eventually leads up to an antigen-specific suppression of the T cell priming. We propose antigen-specific depletion of the pMHCII complexes as a new mechanism for Treg-mediated immune suppression.

For more information go to https://www.niaid.nih.gov/research/immunology-interest-group
Author: Billur Akkaya, MD, D.Phil, NIAID, NIH
CIT Live ID: 35566
Permanent link: https://videocast.nih.gov/watch=35566