International Immunology, Vol. 13, No. 10, 1301-1307,
October 2001
© 2001 Japanese Society for Immunology
MHC class I molecules on adenovirus E1A-expressing tumor cells inhibit NK cell killing but not NK cell-mediated tumor rejection
1 Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206, USA
2 Departments of Medicine and
3 Immunology, and
4 Cancer Center, University of Colorado Health Sciences Center, Denver, CO 80262, USA
5 Department of Medicine, University of California at San Francisco, San Francisco, CA 94113, USA
6 Veterans Affairs Medical Center, San Francisco, CA 94121, USA
Correspondence to: Correspondence to: J. M. Routes, National Jewish Center for Immunology and Respiratory Medicine, Department of Medicine, 1400 Jackson Street, Denver, CO 80206, USA
Expression of adenovirus E1A gene products in tumor cells enhances NK cell lysis in vitro and NK-mediated rejection in vivo, despite increasing class I molecules on tumor cells. It is unclear why the increased expression of MHC class I molecules does not appear to confer resistance to killing by NK cells. One possibility is the unique capacity of E1A to sensitize cells to multiple NK cell killing mechanisms including perforin/granzyme, Fas ligand, tumor necrosis factor-
and TRAIL. To examine this issue, MCA-102-E1A tumor cells (H-2b) that express E1A and are NK sensitive were transfected with H-2Dd, the ligand for the NK inhibitory receptor, Ly49A. Expression of H-2Dd molecules by MCA-102-E1A cells protected them from lysis by a Ly49A+ NK cell clone and Ly49A+ NK cells isolated from C57BL/6 nude mice. In contrast, NK cell-mediated rejection of MCA-102-E1A tumor cells was not inhibited by the expression of H-2Dd molecules, nor was killing by polyclonal populations of NK cells isolated from C57BL/6-nude mice. H-2Dd interacts with several inhibitory Ly49 receptors that are non-clonally expressed on NK cells in C57BL/6 mice: Ly49A (20% of NK cells), Ly49G2 (54% of NK cells) and Ly49C/I (47% of NK cells). Our data indicate that while E1A sensitizes cells to NK cell killing, it does not interfere with signal transduction by inhibitory NK receptors. Therefore, a small population of NK cells that do not express Ly49A, Ly49G2 or Ly49C/I inhibitory receptors are likely responsible for the rejection of MCA-102-E1A-Dd tumor cells in vivo.
Transmitting editor: W. M. Yokoyama
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