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

  • Blood Adv. 2017 Sep 8;1(20):1773-1785. doi: 10.1182/bloodadvances.2017007021.
Anne Zufferey  1 ,  Edwin R Speck  1 ,  Kellie R Machlus  2  3 ,  Rukhsana Aslam  1 ,  Li Guo  1 ,  Mark J McVey  1  4 ,  Michael Kim  1 ,  Rick Kapur  1  5 ,  Eric Boilard  6 ,  Joseph E Italiano Jr  2  3  7 ,  John W Semple  1  5  8  9
Affiliations
  • 1. Toronto Platelet Immunobiology Group, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada.
  • 2. Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, MA.
  • 3. Harvard Medical School, Boston, MA.
  • 4. Departments of Anesthesia and Physiology, University of Toronto, Toronto, ON, Canada.
  • 5. Canadian Blood Services, Toronto, ON, Canada.
  • 6. Centre de Recherche du Centre Hospitalier Universitaire de Québec, Département de Microbiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, QC, Canada.
  • 7. Vascular Biology Program, Department of Surgery, Children's Hospital Boston, Boston, MA.
  • 8. Departments of Pharmacology, Medicine, and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; and.
  • 9. Division of Hematology and Transfusion Medicine, Lund University, Lund, Sweden.
PMID: 29296823 DOI: 10.1182/bloodadvances.2017007021
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.

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