%0 Journal Article
%T Lack of the MHC class II chaperone H2-O causes susceptibility to autoimmune diseases
%A Catherine A. Foss
%A Nianbin Song
%A Robert N. Cole
%A Robin A. Welsh
%A Scheherazade Sadegh-Nasseri
%A Tatiana Boronina
%J -
%D 2020
%R 10.1371/journal.pbio.3000590
%X DO (HLA-DO, in human; murine H2-O) is a highly conserved nonclassical major histocompatibility complex class II (MHC II) accessory molecule mainly expressed in the thymic medulla and B cells. Previous reports have suggested possible links between DO and autoimmunity, Hepatitis C (HCV) infection, and cancer, but the mechanism of how DO contributes to these diseases remains unclear. Here, using a combination of various in vivo approaches, including peptide elution, mixed lymphocyte reaction, T-cell receptor (TCR) deep sequencing, tetramer-guided na£żve CD4 T-cell precursor enumeration, and whole-body imaging, we report that DO affects the repertoire of presented self-peptides by B cells and thymic epithelium. DO induces differential effects on epitope presentation and thymic selection, thereby altering CD4 T-cell precursor frequencies. Our findings were validated in two autoimmune disease models by demonstrating that lack of DO increases autoreactivity and susceptibility to autoimmune disease development
%K T helper cells
%K T cells
%K Mouse models
%K B cells
%K Central nervous system
%K Antigen-presenting cells
%K Regulatory T cells
%K Autoimmune diseases
%U https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000590