期刊
JOURNAL OF IMMUNOLOGY
卷 207, 期 9, 页码 2255-2264出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.2001426
关键词
-
类别
资金
- Department of Health Australia, National Health and Medical Research Council [1058193, 1113293, 1154502, 1163090, 1161101, 1129672]
- Department of Education and Training, Australian Research Council (ARC) [160103134, 170102471, 190102213, 190101242, 180100844, 160101373, 180100521]
- Human Frontiers Science Program grant [0064/2011]
- Australian Government's National Health and Medical Research Council Victorian State Government Operational Infrastructure Support
- Independent Research Institutes Infrastructure Support Scheme
- Russell and Mab Grimwade Miegunyah Fund at the University of Melbourne
- ARC Discovery Early Career Researcher Award Fellowship (ARC) [DE180100418]
- National Health and Medical Research Council of Australia [1163090, 1161101, 1129672, 1058193] Funding Source: NHMRC
Ubiquitination of MHC II in dendritic cells affects the homeostasis, phenotype, cytokine production, and antigen proteolysis by DCs, with consequences for antigen presentation, T cell responses, and antibody-mediated immunity.
MHC class II (MHC II) Ag presentation by dendritic cells (DCs) is critical for CD4(+) 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 IIKRKI/KI 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 IIKRKI/KI spleen, with the remaining MHC IIKRKI/KI DCs expressing an altered surface phenotype. Whereas Ag uptake, endosomal pH, and cathepsin protease activity were unaltered, MHC IIKRKI/KI cDC1 produced increased inflammatory cytokines and possessed defects in Ag proteolysis. Immunization of MHC IIKRKI/KI 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 IIKRKI/KI mice following immunization with cell-associated and anti-Clec9AOVA. Immunization of MHC IIKRKI/KI mice failed to elicit follicular Th cell responses and generated barely detectable Ab to antiClec9A 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据