Mouse Homologue of Human HLA-DO Does Not Preempt Autoimmunity but Controls Murine Gammaherpesvirus MHV68. J Immunol 2021 Dec 15;207(12):2944-2951
Date
11/24/2021Pubmed ID
34810225Pubmed Central ID
PMC9124240DOI
10.4049/jimmunol.2100650Scopus ID
2-s2.0-85134177854 (requires institutional sign-in at Scopus site)Abstract
H2-O (human HLA-DO) is a relatively conserved nonclassical MHC class II (MHCII)-like molecule. H2-O interaction with human HLA-DM edits the repertoire of peptides presented to TCRs by MHCII. It was long hypothesized that human HLA-DM inhibition by H2-O provides protection from autoimmunity by preventing binding of the high-affinity self-peptides to MHCII. The available evidence supporting this hypothesis, however, was inconclusive. A possibility still remained that the effect of H2-O deficiency on autoimmunity could be better revealed by using H2-O-deficient mice that were already genetically predisposed to autoimmunity. In this study, we generated and used autoimmunity-prone mouse models for systemic lupus erythematosus and organ-specific autoimmunity (type 1 diabetes and multiple sclerosis) to definitively test whether H2-O prevents autoimmune pathology. Whereas our data failed to support any significance of H2-O in protection from autoimmunity, we found that it was critical for controlling a γ-herpesvirus, MHV68. Thus, we propose that H2-O editing of the MHCII peptide repertoire may have evolved as a safeguard against specific highly prevalent viral pathogens.
Author List
Lee J, Cullum E, Stoltz K, Bachmann N, Strong Z, Millick DD, Denzin LK, Chang A, Tarakanova V, Chervonsky AV, Golovkina TAuthor
Vera Tarakanova PhD Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntigen Presentation
Autoimmunity
HLA-D Antigens
Histocompatibility Antigens Class II
Humans
Mice
Peptides
Receptors, Antigen, T-Cell
