First Author | Welsh RA | Year | 2020 |
Journal | PLoS Biol | Volume | 18 |
Issue | 2 | Pages | e3000590 |
PubMed ID | 32069316 | Mgi Jnum | J:285329 |
Mgi Id | MGI:6392481 | Doi | 10.1371/journal.pbio.3000590 |
Citation | Welsh RA, et al. (2020) Lack of the MHC class II chaperone H2-O causes susceptibility to autoimmune diseases. PLoS Biol 18(2):e3000590 |
abstractText | 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 naive 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. |