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MHC Class II Ubiquitination Regulates Dendritic Cell Function and Immunity.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2021 Nov 01; Vol. 207 (9), pp. 2255-2264. Date of Electronic Publication: 2021 Oct 01. - Publication Year :
- 2021
-
Abstract
- MHC class II (MHC II) Ag presentation by dendritic cells (DCs) is critical for CD4 <superscript>+</superscript> T cell immunity. Cell surface levels of MHC II loaded with peptide is controlled by ubiquitination. In this study, we have examined how MHC II ubiquitination impacts immunity using MHC IIKR <superscript>KI/KI</superscript> mice expressing mutant MHC II molecules that are unable to be ubiquitinated. Numbers of conventional DC (cDC) 1, cDC2 and plasmacytoid DCs were significantly reduced in MHC IIKR <superscript>KI/KI</superscript> spleen, with the remaining MHC IIKR <superscript>KI/KI</superscript> DCs expressing an altered surface phenotype. Whereas Ag uptake, endosomal pH, and cathepsin protease activity were unaltered, MHC IIKR <superscript>KI/KI</superscript> cDC1 produced increased inflammatory cytokines and possessed defects in Ag proteolysis. Immunization of MHC IIKR <superscript>KI/KI</superscript> mice identified impairments in MHC II and MHC class I presentation of soluble, cell-associated and/or DC-targeted OVA via mAb specific for DC surface receptor Clec9A (anti-Clec9A-OVA mAb). Reduced T cell responses and impaired CTL killing was observed in MHC IIKR <superscript>KI/KI</superscript> mice following immunization with cell-associated and anti-Clec9A-OVA. Immunization of MHC IIKR <superscript>KI/KI</superscript> mice failed to elicit follicular Th cell responses and generated barely detectable Ab to anti-Clec9A mAb-targeted Ag. In summary, MHC II ubiquitination in DCs impacts the homeostasis, phenotype, cytokine production, and Ag proteolysis by DCs with consequences for Ag presentation and T cell and Ab-mediated immunity.<br /> (Copyright © 2021 by The American Association of Immunologists, Inc.)
- Subjects :
- Animals
Antigen Presentation genetics
Cells, Cultured
Cytotoxicity, Immunologic
Histocompatibility Antigens Class II genetics
Immunity, Cellular
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Mice, Transgenic
Mutation genetics
Ubiquitination
CD4-Positive T-Lymphocytes immunology
Dendritic Cells immunology
Germinal Center immunology
Histocompatibility Antigens Class II metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 207
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 34599081
- Full Text :
- https://doi.org/10.4049/jimmunol.2001426