Regulatory T Cells Mediate Specific Suppression by Depleting Peptide-MHC Class II from Dendritic Cells

Overview

Journal Nat Immunol

Date 2019 Jan 16

PMID 30643268

Citations 118

Authors

Billur Akkaya

Yoshihiro Oya

Munir Akkaya

Jafar Al Souz

Amanda H Holstein

Olena Kamenyeva

Juraj Kabat

Ryutaro Matsumura

David W Dorward

Deborah D Glass

Ethan M Shevach

Affiliations

Soon will be listed here.

Abstract

Regulatory T cells (T cells) can activate multiple suppressive mechanisms in vitro after activation via the T cell antigen receptor, resulting in antigen-independent suppression. However, it remains unclear whether similar pathways operate in vivo. Here we found that antigen-specific T cells activated by dendritic cells (DCs) pulsed with two antigens suppressed conventional naive T cells (T cells) specific for both cognate antigens and non-cognate antigens in vitro but suppressed only T cells specific for cognate antigen in vivo. Antigen-specific T cells formed strong interactions with DCs, resulting in selective inhibition of the binding of T cells to cognate antigen yet allowing bystander T cell access. Strong binding resulted in the removal of the complex of cognate peptide and major histocompatibility complex class II (pMHCII) from the DC surface, reducing the capacity of DCs to present antigen. The enhanced binding of T cells to DCs, coupled with their capacity to deplete pMHCII, represents a novel pathway for T cell-mediated suppression and may be a mechanism by which T cells maintain immune homeostasis.

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