Abstract
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-gamma 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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antibodies, Blocking / pharmacology
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Antigens, CD1 / administration & dosage*
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Antigens, CD1 / biosynthesis
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Antigens, CD1 / genetics*
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Antigens, CD1 / physiology
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Antigens, CD1d
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Cells, Cultured
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Cytotoxicity, Immunologic / genetics
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Epitopes, T-Lymphocyte / immunology
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Female
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Graft Survival / genetics*
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Graft Survival / immunology
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H-2 Antigens / genetics
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Histocompatibility Antigens / administration & dosage*
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Histocompatibility Antigens / biosynthesis
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Histocompatibility Antigens / genetics*
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Histocompatibility Antigens / physiology
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Humans
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Immune Sera / pharmacology
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Immunophenotyping
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Intercellular Adhesion Molecule-1 / immunology
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Intercellular Adhesion Molecule-1 / metabolism
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Jurkat Cells
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K562 Cells
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L Cells
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Lymphocyte Activation / genetics
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Lymphocyte Function-Associated Antigen-1 / immunology
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Lymphocyte Function-Associated Antigen-1 / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Inbred CBA
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Mice, Transgenic
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Skin Transplantation / immunology
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T-Lymphocytes, Cytotoxic / immunology
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T-Lymphocytes, Cytotoxic / metabolism
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Transfection
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U937 Cells
Substances
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Antibodies, Blocking
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Antigens, CD1
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Antigens, CD1d
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CD1D protein, human
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Epitopes, T-Lymphocyte
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H-2 Antigens
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H-2Kb protein, mouse
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Histocompatibility Antigens
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Immune Sera
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Lymphocyte Function-Associated Antigen-1
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Intercellular Adhesion Molecule-1