An in vivo model of the human CD1 antigen presenting system (42.24)

Abstract CD1 molecules are a family of antigen presenting molecules that present lipids and glycolipids for recognition by specialized T cells. The CD1 system has been implicated in microbial infections, autoimmune and allergic disorders, and immunological control of tumors. However, our understanding of its role in human disease remains limited because animal models that resemble the human CD1 system are lacking. Here we report that a severely immune deficient mouse engrafted with human fetal tissues and hematopoietic stem cells develops an intact human CD1 antigen presenting system. Human CD1a, b, c, and d isoforms are highly expressed in the thymic organoid that develops in the engrafted mice, and histological analysis indicates the presence of CD1a+ APCs. Moreover, CD1+ APCs are expressed in peripheral tissues including the spleen and liver, and are capable of presenting bacterial glycolipids to human T cells specific for CD1a, b, or c. Staining with CD1d tetramers detected comparable percentages of human CD1d-restricted T cells in engrafted mice and human blood, and CD1d-restricted T cells isolated from the mice expressed a characteristic Vα24+/Vβ11+ TCR and recognized the glycolipid antigen α-GalCer. These results demonstrate the functional reconstitution of the human CD1 system in a mouse model.