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Human CD1d Functions as a Transplantation Antigen and a Restriction Element in Mice¹

Bin Wang^*, Taehoon Chun^*, Ingrid C. Rulifson, Mark Exley, Steven P. Balk and Chyung-Ru Wang^2,*

^* Gwen Knapp Center for Lupus and Immunology Research, Committee on Immunology and Department of Pathology, and Ben May Institute for Cancer Research, University of Chicago, Chicago, IL 60637; and Cancer Biology Program, Hematology/Oncology Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215

To study the potential functions of human CD1d (hCD1d), we developed transgenic (Tg) mice that ectopically express hCD1d under the control of H-2K^b promoter. High levels of hCD1d expression were detected in all Tg tissues tested. Skin grafts from the K^b/hCD1d Tg mice were rapidly rejected by MHC-matched non-Tg recipient mice, suggesting that hCD1d can act as transplantation Ags. Furthermore, we were able to elicit hCD1d-restricted CD8⁺ CTLs from mice immunized with K^b/hCD1d Tg splenocytes. These CTLs express TCR rearrangements that are distinct from invariant TCR of NK T cells, and secrete significant amounts of IFN- upon Ag stimulation. Analysis with various hCD1d-expressing targets and use of Ag presentation inhibitors indicated the recognition of hCD1d by CTLs did not involve species or tissue-specific ligands nor require the processing pathways of endosomes or proteasomes. Additionally, the reactivity of hCD1d-specific CTLs was not affected by acid stripping followed by brefeldin A treatment, suggesting that CTLs may recognize a ligand/hCD1d complex that is resistant to acid denaturation, or empty hCD1d molecules. Our results show that hCD1d can function as an alloantigen for CD8⁺ CTLs. The hCD1d Tg mice provide a versatile model for the study of hCD1d-restricted cytolytic responses to microbial Ags.

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