CD66a interactions between human melanoma and NK cells: a novel class I MHC-independent inhibitory mechanism of cytotoxicity.
NK cells are able to kill virus-infected and tumor cells via a panel of lysis receptors. Cells expressing class I MHC proteins are protected from lysis primarily due to the interactions of several families of NK receptors with both classical and nonclassical class I MHC proteins. In this study we show that a class I MHC-deficient melanoma cell line (1106mel) is stained with several Ig-fused lysis receptors, suggesting the expression of the appropriate lysis ligands. Surprisingly, however, this melanoma line was not killed by CD16-negative NK clones. The lack of killing is shown to be the result of homotypic CD66a interactions between the melanoma line and the NK cells. Furthermore, 721.221 cells expressing the CD66a protein were protected from lysis by YTS cells and by NK cells expressing the CD66a protein. Redirected lysis experiments demonstrated that the strength of the inhibitory effect is correlated with the levels of CD66a expression. Finally, the expression of CD66a protein was observed on NK cells derived from patients with malignant melanoma. These findings suggest the existence of a novel class I MHC-independent inhibitory mechanism of human NK cell cytotoxicity. This may be a mechanism that is used by some of the class I MHC-negative melanoma cells to evade attack by CD66a-positive NK cells.
Markel
Gal
G
Lautenberg Center for General and Tumor Immunology and Sharet Institute of Oncology, Hadassah Medical School, Jerusalem, Israel.
Lieberman
Niva
N
Katz
Gil
G
Arnon
Tal I
TI
Lotem
Michal
M
Drize
Olga
O
Blumberg
Richard S
RS
Bar-Haim
Erez
E
Mader
Reuven
R
Eisenbach
Lea
L
Mandelboim
Ofer
O
D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015815:Cell Adhesion Molecules; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007165:Immunosuppression Therapy; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008024:Ligands; D008545:Melanoma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017452:Receptors, IgG / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000943:Antigens, Differentiation; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D017452:Receptors, IgG