Lack of the MHC class II chaperone H2-O causes susceptibility to autoimmune diseases.
Animals
Antigen-Presenting Cells
/ immunology
Autoimmune Diseases
/ genetics
Autoimmunity
/ genetics
B-Lymphocytes
/ immunology
CD4-Positive T-Lymphocytes
/ immunology
Collagen
/ administration & dosage
Disease Models, Animal
Genetic Predisposition to Disease
/ genetics
Histocompatibility Antigens Class II
/ genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Myelin-Oligodendrocyte Glycoprotein
/ immunology
Peptides
/ immunology
Precursor Cells, T-Lymphoid
/ immunology
Thymus Gland
/ immunology
Journal
PLoS biology
ISSN: 1545-7885
Titre abrégé: PLoS Biol
Pays: United States
ID NLM: 101183755
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
26
07
2019
accepted:
13
01
2020
entrez:
19
2
2020
pubmed:
19
2
2020
medline:
15
5
2020
Statut:
epublish
Résumé
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 naïve 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.
Identifiants
pubmed: 32069316
doi: 10.1371/journal.pbio.3000590
pii: PBIOLOGY-D-19-02166
pmc: PMC7028248
doi:
Substances chimiques
H-2O antigen
0
Histocompatibility Antigens Class II
0
Myelin-Oligodendrocyte Glycoprotein
0
Peptides
0
Collagen
9007-34-5
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e3000590Subventions
Organisme : NIAID NIH HHS
ID : R01 AI063764
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI120634
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI101987
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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