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

Research output: Contribution to journalArticle

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 CD342 MHC class II2 CD411 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 CD81 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 CD81 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 CD81 T-cell responses via antigen presentation and are able to spread this immunogenic information through platelets.

Details

Authors
  • Anne Zufferey
  • Edwin R Speck
  • Kellie R Machlus
  • Rukhsana Aslam
  • Li Guo
  • Mark J McVey
  • Michael Kim
  • Rick Kapur
  • Eric Boilard
  • Joseph E. Italiano Jr.
  • John W Semple
Organisations
External organisations
  • Saint Michael's Hospital
  • Harvard Medical School
  • University of Toronto
  • Laval University
  • Canadian Blood Services
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area
Original languageEnglish
Pages (from-to)1773-1785
Number of pages13
JournalBlood Advances
Volume1
Issue number20
Publication statusPublished - 2017
Publication categoryResearch
Peer-reviewedYes