Human CD1d functions as a transplantation antigen and a restriction element in mice.
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.
Gwen Knapp Center for Lupus and Immunology Research, Committee on Immunology and Department of Pathology, University of Chicago, Chicago, IL 60637, USA. cwang@midway.uchicago.edu
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D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D018949:Antigens, CD1 / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D055610:Antigens, CD1d; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006085:Graft Survival / Q000235:genetics* / Q000276:immunology; D006183:H-2 Antigens / Q000235:genetics; D006649:Histocompatibility Antigens / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D016130:Immunophenotyping; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D019169:Jurkat Cells; D020014:K562 Cells; D007739:L Cells; D008213:Lymphocyte Activation / Q000235:genetics; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D016038:Skin Transplantation / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D020298:U937 Cells
D019138:Antibodies, Blocking; D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D006649:Histocompatibility Antigens; D007106:Immune Sera; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1