Journal
BLOOD ADVANCES
Volume 1, Issue 20, Pages 1773-1785Publisher
ELSEVIER
DOI: 10.1182/bloodadvances.2017007021
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Funding
- Health Canada
- Canadian Blood Services (CBS)
- CBS Graduate Research Fellowship
- National Institutes of Health, National Heart, Lung, and Blood Institute [5F32HL118865]
- National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases [1K01DK111515]
- Swiss National Science Foundation [P300PB_164760]
- CBS
- Ontario Trillium Scholarship
- China Scholarship Council
- Swiss National Science Foundation (SNF) [P300PB_164760] Funding Source: Swiss National Science Foundation (SNF)
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Megakaryocytes (MKs) are bone marrow-derived cells that are primarily responsible for generating platelets for the maintenance of hemostasis. Although MK can variably express major histocompatibility complex (MHC) class I and II molecules during their differentiation, little is known whether they can elicit nonhemostatic immune functions such as T-cell activation. Here, we demonstrate that mature CD34(-) MHC class II- CD41(+) MKs can endocytose exogenous ovalbumin (OVA) and proteolytically generate its immunogenic peptide ligand, which is crosspresented on their surface in association with MHC class I molecules. This crosspresentation triggered in vitro and in vivo OVA-specific CD8(+) T-cell activation and proliferation. In addition, the OVA-MHC class I complexes were transferred from MK to pro-platelets upon thrombopoiesis in vitro. MK could also present endogenous MK-associated (CD61) peptides to activate CD61-specific CD8(+) T cells and mediate immune thrombocytopenia in vivo. These results suggest that, in addition to their hemostatic role, mature MKs can significantly affect antigen-specific CD8(+) T-cell responses via antigen presentation and are able to spread this immunogenic information through platelets.
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