Anti-HLA Class I Antibodies Alter Gene Expression in Human Natural Killer Cells

Abstract

Natural killer (NK) function can be augmented by a variety of agents, including interleukin 2 (IL2) and interferon (IFN) (1–3). Anti-HLA class I and anti-LFA-1 monoclonal antibodies (MAbs) also affect NK lysis at the level of the effector cell (4–8). These modulators were used to assess potential changes in gene expression in a human NK clone (NK3.3) associated with activation or inhibition of lytic function. We have found that augmentation of NK3.3 lysis by IL2, IFN-β, and the anti-HLA A-locus-specific MAb 131 (9) is associated with increased levels of message encoding the proto-oncogene c-myb. Conversely, inhibition of lysis by the anti-HLA A,B,C-specific MAb W6/32 (10) results in decreased c-myb expression. The anti-LFA-1 MAb ICII (8), which inhibits the lysis of K562 but not of MOLT-4 target cells by NK3.3, has no effect on c-myb expression. These results indicate that anti-HLA class I MAbs alter gene expression in NK cells and that c-myb expression may be associated with NK lytic function.