CD36 Mediates Cell-Surface Antigens to Promote Thymic Development of the Regulatory T Cell Receptor Repertoire and Allo-tolerance

The development of T cell tolerance in the thymus requires the presentation of host proteins by multiple antigen-presenting cell (APC) types. However, the importance of transferring host antigens from transcription factor AIRE-dependent medullary thymic epithelial cells (mTECs) to bone marrow (BM) APCs is unknown. We report that antigen was primarily transferred from mTECs to CD8α⁺ dendritic cells (DCs) and showed that CD36, a scavenger receptor selectively expressed on CD8α⁺ DCs, mediated the transfer of cell-surface, but not cytoplasmic, antigens. The absence of CD8α⁺ DCs or CD36 altered thymic T cell selection, as evidenced by TCR repertoire analysis and the loss of allo-tolerance in murine allogeneic BM transplantation (allo-BMT) studies. Decreases in these DCs and CD36 expression in peripheral blood of human allo-BMT patients correlated with graft-versus-host disease. Our findings suggest that CD36 facilitates transfer of mTEC-derived cell-surface antigen on CD8α⁺ DCs to promote tolerance to host antigens during homeostasis and allo-BMT. How cooperative antigen presentation between medullary thymic epithelial cells (mTECs) and dendritic cells (DCs) occurs remains unknown. Perry et al. show that CD36, a scavenger receptor expressed on CD8α⁺ DCs, mediates acquisition and presentation of cell-surface antigens from mTECs for T cell receptor repertoire development and allo-tolerance during bone marrow transplantation.