CD66a interactions between human melanoma and NK cells: A novel class I MHC-independent inhibitory mechanism of cytotoxicity

Gal Markel, Niva Lieberman, Gil Katz, Tal I. Arnon, Michal Lotem, Olga Drize, Richard S. Blumberg, Erez Bar-Haim, Reuven Mader, Lea Eisenbach, Ofer Mandelboim

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)2803-2810
Number of pages8
JournalJournal of Immunology
Volume168
Issue number6
DOIs
StatePublished - 15 Mar 2002
Externally publishedYes

Fingerprint

Dive into the research topics of 'CD66a interactions between human melanoma and NK cells: A novel class I MHC-independent inhibitory mechanism of cytotoxicity'. Together they form a unique fingerprint.

Cite this