MHC II-expressing bone marrow megakaryocytes are noncanonical antigen-presenting cells and activate CD4+ T cells ex vivo
While professional antigen-presenting cells drive adaptive immunity, atypical cell types can fulfill this role in the bone marrow. Megakaryocytes (MKs) are canonically recognized for platelet production, but recent studies indicate functional heterogeneity and immune potential. We found that ∼20% of bone marrow MKs express major histocompatibility complex (MHC) II and co-stimulatory receptors CD80, CD86, CD40, and CD83. These MKs process and present antigen to activate T cells ex vivo in an MHC II-dependent manner. MK/T cell interactions induced TGF-β1 secretion and promoted induced regulatory T cell (Treg) differentiation. Toll-like receptor (TLR) stimulation of MKs elicited modest Th1-associated responses, including IFN-γ and TNF-α production, without robust Th17 differentiation. Immunopeptidomics confirmed peptide occupancy of MK MHC II in vivo . Using MK-targeted MHC II deletion, we observed altered TLR responses and reduced bone marrow TGF-β1. Together, these findings identify MHC II+ MKs as noncanonical antigen-presenting cells with potential roles in regulating CD4 + T cell responses within the bone marrow niche.
Authors
- Vijay G. Sankaran (ORCID: https://orcid.org/0000-0003-0044-443X)
- Montserrat Carrascal (ORCID: https://orcid.org/0000-0002-0205-2176)
- Marcelo Falchetti (ORCID: https://orcid.org/0000-0002-9438-680X)
- Kellie R. Machlus (ORCID: https://orcid.org/0000-0002-2155-1050)
- Jaxaira Maggi (ORCID: https://orcid.org/0000-0002-1214-8761)
- Isabelle C. Becker (ORCID: https://orcid.org/0000-0003-2725-8493)
- Pavel Hanč (ORCID: https://orcid.org/0000-0002-0511-5566)
- Chen Weng (ORCID: https://orcid.org/0009-0003-4351-3340)
- Joseph E. Italiano (ORCID: https://orcid.org/0000-0001-6547-9663)
- Mahmoud Adel Bassal (ORCID: https://orcid.org/0000-0003-4322-2968)
- Estelle Carminita (ORCID: https://orcid.org/0000-0002-8544-4879)
- Ulrich H. von Andrian (ORCID: https://orcid.org/0000-0003-4231-2283)
- Virginia Camacho (ORCID: https://orcid.org/0000-0002-6970-0932)
- Karen G. Wang
- María N. Barrachina (ORCID: https://orcid.org/0000-0002-1701-6899)
- Dong H. Lee
- Deepa Gautam
Institutions
- Broad Institute (US)
- Brigham and Women's Hospital (US)
- Boston Children's Hospital (US)
- Howard Hughes Medical Institute (US)
- Consejo Superior de Investigaciones Científicas (ES)
- Harvard University (US)
- Ragon Institute of MGH, MIT and Harvard (US)
- Massachusetts General Hospital (US)
- Dana-Farber Cancer Institute (US)
- Institut d'Investigacions Biomèdiques de Barcelona (ES)
- Whitehead Institute for Biomedical Research (US)
- Harvard Stem Cell Institute (US)
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
- Massachusetts Institute of Technology (US)
Publication Details
- Journal
- Cell Reports
- Published
- 2026-10-30
- DOI
- https://doi.org/10.1016/j.celrep.2026.118230
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Howard Hughes Medical Institute
- American Heart Association
- American Society of Hematology
- National Heart, Lung, and Blood Institute
- National Cancer Institute
- National Institute of Diabetes and Digestive and Kidney Diseases