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

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.

HSP90α deficiency does not affect immunoglobulin gene hypermutation and class switch but causes enhanced MHC class II antigen presentation.

Heat shock protein 90 (HSP90) is a molecular chaperone required for efficient antigen presentation and cross-presentation. In addition, HSP90 was recently reported to interact with and stabilize the activation-induced cytidine deaminase (AID) and plays a critical role in immunoglobulin gene hypermutation and class switch recombination. In mice and humans, there are two HSP90 isoforms, HSP90α and HSP90β, but the in vivo role of each isoform remains largely unknown.