Monoclonal antibodies against human Ia antigens stimulate monocytes to secrete interleukin 1

The monoclonal antibodies (mAb) DA6.147, DA6.164, and HIG.48 against human Ia antigens, but not the W6/32 mAb against human class I major histocompatibility complex antigens or the anti-monocyte OKM1 and 63D3 mAb, stimulated monocytes to secrete interleukin 1 (IL-1). IL-1 was measured by its property of promoting the production of interleukin 2 (IL-2) by phytohemagglutinin-treated LBRM-33 clone 1A5 cells. IL-1 activity induced by anti-Ia antibodies could be detected 24 hr after initiation of the cultures and reached its highest levels at days 3-4 of culture. Concentrations of 1 microgram/ml or higher of the anti-Ia antibodies induced monocytes to secrete significant levels of IL-1 activity. The anti-Ia mAb induced Ia-bearing but not Ia-negative monocytes to secrete IL-1. Both Ia-positive and Ia-negative monocytes produced IL-1 activity under the stimulus of lipopolysaccharide. It is concluded that the DA6.147, DA6.164, and HIG.48 mAb stimulate secretion of IL-1 by interacting Ia antigens on monocytes. The data support the view that besides serving as restricting elements for recognition of foreign antigens by T cells, Ia antigens may also function as transducer elements.