Loss of MHC II ubiquitination inhibits the activation and differentiation of CD4 T cells.

Abstract:

:Peptide-MHC class II complexes (pMHC II) are degraded by MARCH-I-mediated ubiquitination, and the stabilization of pMHC II by loss of its ubiquitination is one phenotype defining the activation of conventional dendritic cells (cDCs). However, the role of such stabilization of pMHC II in the context of T-cell activation/differentiation remains unclear. Here, we show that loss of pMHC II ubiquitination inhibits the activation and differentiation of CD4 T cells, probably through down-regulation of CD18/integrin β2 and their diminished IL-12 production in a cell intrinsic manner. The cDCs generated from mice whose pMHC II ubiquitination is inhibited had a decreased ability to activate naive CD4 T cells and induce Th1/Th17 differentiation. In addition, cDCs whose MHC II ubiquitination was inhibited showed down-regulation of CD18/integrin beta 2 and of IL-12 production. This unexpected finding suggests that loss of MHC II ubiquitination contributes to the negative feedback of CD4 T-cell immune responses.

journal_name

Int Immunol

journal_title

International immunology

authors

Ishikawa R,Kajikawa M,Ishido S

doi

10.1093/intimm/dxt066

subject

Has Abstract

pub_date

2014-05-01 00:00:00

pages

283-9

issue

5

eissn

0953-8178

issn

1460-2377

pii

dxt066

journal_volume

26

pub_type

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