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

Zufferey, Anne ; Speck, Edwin R ; Machlus, Kellie R ; Aslam, Rukhsana ; Guo, Li ; McVey, Mark J ; Kim, Michael ; Kapur, Rick LU ; Boilard, Eric and Italiano Jr., Joseph E. , et al. (2017) In Blood Advances 1(20). p.1773-1785
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... (More)

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.

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Blood Advances
volume
1
issue
20
pages
13 pages
publisher
American Society of Hematology
external identifiers
  • scopus:85044241255
  • scopus:85044241255
ISSN
2473-9529
DOI
10.1182/bloodadvances.2017007021
language
English
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yes
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97fda153-0dc6-4468-8d1f-b4e973befc84
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2017-12-21 12:24:12
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2020-04-01 06:28:07
@article{97fda153-0dc6-4468-8d1f-b4e973befc84,
  abstract     = {<p>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>2</sup> MHC class II<sup>2</sup> CD41<sup>1</sup> 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<sup>1</sup> 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<sup>1</sup> 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<sup>1</sup> T-cell responses via antigen presentation and are able to spread this immunogenic information through platelets.</p>},
  author       = {Zufferey, Anne and Speck, Edwin R and Machlus, Kellie R and Aslam, Rukhsana and Guo, Li and McVey, Mark J and Kim, Michael and Kapur, Rick and Boilard, Eric and Italiano Jr., Joseph E. and Semple, John W},
  issn         = {2473-9529},
  language     = {eng},
  number       = {20},
  pages        = {1773--1785},
  publisher    = {American Society of Hematology},
  series       = {Blood Advances},
  title        = {Mature murine megakaryocytes present antigen-MHC class I molecules to T cells and transfer them to platelets},
  url          = {http://dx.doi.org/10.1182/bloodadvances.2017007021},
  doi          = {10.1182/bloodadvances.2017007021},
  volume       = {1},
  year         = {2017},
}