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Mature murine megakaryocytes present antigen-MHC class I molecules to T cells and transfer them to platelets.


ABSTRACT: 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.

SUBMITTER: Zufferey A 

PROVIDER: S-EPMC5728336 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Mature murine megakaryocytes present antigen-MHC class I molecules to T cells and transfer them to platelets.

Zufferey Anne A   Speck Edwin R ER   Machlus Kellie R KR   Aslam Rukhsana R   Guo Li L   McVey Mark J MJ   Kim Michael M   Kapur Rick R   Boilard Eric E   Italiano Joseph E JE   Semple John W JW  

Blood advances 20170908 20


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<sup>-</sup> MHC class II<sup>-</sup> CD41<sup>+</sup> MKs can endocytose exogenous ovalbumin (O  ...[more]

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