Mouse Homologue of Human HLA-DO Does Not Preempt Autoimmunity but Controls Murine Gammaherpesvirus MHV68.
Journal
Journal of immunology (Baltimore, Md. : 1950)
ISSN: 1550-6606
Titre abrégé: J Immunol
Pays: United States
ID NLM: 2985117R
Informations de publication
Date de publication:
15 12 2021
15 12 2021
Historique:
received:
07
07
2021
accepted:
14
10
2021
pubmed:
24
11
2021
medline:
14
7
2022
entrez:
23
11
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34810225
pii: jimmunol.2100650
doi: 10.4049/jimmunol.2100650
pmc: PMC9124240
mid: NIHMS1749455
doi:
Substances chimiques
HLA-D Antigens
0
Histocompatibility Antigens Class II
0
Peptides
0
Receptors, Antigen, T-Cell
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2944-2951Subventions
Organisme : NIAID NIH HHS
ID : R01 AI117535
Pays : United States
Informations de copyright
Copyright © 2021 by The American Association of Immunologists, Inc.
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