Inhibition of human NK cell-mediated killing by CD1 molecules.
It is now well established that NK cells recognize classical and nonclassical MHC class I molecules and that such recognition typically results in the inhibition of target cell lysis. Given the known structural similarities between MHC class I and non-MHC-encoded CD1 molecules, we investigated the possibility that human CD1a, -b, and -c proteins might also function as specific target structures for NK cell receptors. Here we report that expression of CD1a, -b, or -c can partially inhibits target cell lysis by freshly isolated human NK cells and cultured NK lines. The inhibitory effects of CD1 molecules on NK cell could be shown upon expression of individual CD1 proteins in transfected NK-sensitive target cells, and these effects could be reversed by incubation of the target cells with mAbs specific for the expressed form of CD1. Inhibitory effects of CD1 expression on NK-mediated lysis could also be shown for cultured human dendritic cells, which represent a cell type that prominently expresses the various CD1 proteins in vivo. In addition, the bacterial glycolipid Ags known to be bound and presented by CD1 proteins could significantly augment the observed inhibitory effects on target cell lysis by NK cells.
Carbone
E
E
Microbiology and Tumorbiology Center, Karolinska Institutet, Stockholm, Sweden. ennio.carbone@mtc.ki.se
Terrazzano
G
G
Melián
A
A
Zanzi
D
D
Moretta
L
L
Porcelli
S
S
Kärre
K
K
Zappacosta
S
S
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000942:Antigens, Bacterial / Q000494:pharmacology; D018949:Antigens, CD1 / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism*; D002460:Cell Line; D002999:Clone Cells; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D006017:Glycolipids / Q000276:immunology; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D007108:Immune Tolerance; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D008024:Ligands; D008055:Lipids / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology; D014162:Transfection
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D018949:Antigens, CD1; D006017:Glycolipids; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D008055:Lipids