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

Area of Science:

• Immunology
• Hematology
• Cell Biology

Background:

• Megakaryocytes (MKs) are crucial for platelet production and hemostasis.
• The non-hemostatic immune functions of MKs, particularly T-cell activation, remain largely unexplored.
• While MKs express MHC molecules, their capacity for antigen presentation is not well understood.

Purpose of the Study:

• To investigate the potential of mature MKs to present exogenous and endogenous antigens.
• To determine if MKs can activate antigen-specific CD8+ T cells.
• To explore the role of MKs in immune responses beyond platelet generation.

Main Methods:

• Utilized flow cytometry and immunofluorescence to characterize mature MKs.
• Employed ovalbumin (OVA) and CD61 peptides for antigen presentation assays.
• Assessed T-cell activation and proliferation in vitro and in vivo models.
• Investigated antigen-MHC complex transfer during thrombopoiesis.

Main Results:

• Mature MKs efficiently endocytose exogenous antigens (e.g., OVA) and crosspresent their peptides via MHC class I molecules.
• OVA-MHC class I complexes on MKs activate and promote proliferation of OVA-specific CD8+ T cells both in vitro and in vivo.
• MKs present endogenous CD61 peptides, activating CD61-specific CD8+ T cells and inducing immune thrombocytopenia in vivo.
• Antigen-MHC complexes are transferred from MKs to pro-platelets during thrombopoiesis.

Conclusions:

• Mature MKs possess potent antigen-presenting cell capabilities, extending their function beyond hemostasis.
• MKs play a significant role in initiating and modulating antigen-specific CD8+ T-cell responses.
• Platelets can serve as vehicles for spreading immunogenic information originating from MKs, potentially impacting adaptive immunity.